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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

PPARγ Agonists in Combination Cancer Therapies

Author(s): Piotr Mrowka and Eliza Glodkowska-Mrowka*

Volume 20, Issue 3, 2020

Page: [197 - 215] Pages: 19

DOI: 10.2174/1568009619666191209102015

Price: $65


Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. These unique properties constitute a strong therapeutic potential that place PPARγ agonists as one of the most interesting and widely studied anticancer molecules.

Although PPARγ agonists exert significant, antiproliferative and tumoricidal activity in vitro, their anticancer efficacy in animal models is ambiguous, and their effectiveness in clinical trials in monotherapy is unsatisfactory. However, due to pleiotropic effects of PPARγ activation in normal and tumor cells, PPARγ ligands interact with many antitumor treatment modalities and synergistically potentiate their effectiveness. The most spectacular example is a combination of PPARγ ligands with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In this setting, PPARγ activation sensitizes leukemic stem cells, resistant to any previous form of treatment, to targeted therapy. Thus, this combination is believed to be the first pharmacological therapy able to cure CML patients.

Within the last decade, a significant body of data confirming the benefits of the addition of PPARγ ligands to various antitumor therapies, including chemotherapy, hormonotherapy, targeted therapy, and immunotherapy, has been published. Although the majority of these studies have been carried out in vitro or animal tumor models, a few successful attempts to introduce PPARγ ligands into anticancer therapy in humans have been recently made. In this review, we aim to summarize shines and shadows of targeting PPARγ in antitumor therapies.

Keywords: Peroxisome proliferator-activated receptor-gamma, PPARγ ligand, thiazolidinediones, cancer, leukemia, combination therapy, tyrosine kinase inhibitors, imatinib.

Graphical Abstract
Choi, S.H.; Chung, S.S.; Park, K.S. Re-highlighting the action of PPARγ in treating metabolic diseases. F1000 Res., 2018, 7, 7.
[] [PMID: 30079233]
Greene, M.E.; Blumberg, B.; McBride, O.W.; Yi, H.F.; Kronquist, K.; Kwan, K.; Hsieh, L.; Greene, G.; Nimer, S.D. Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr., 1995, 4(4-5), 281-299.
[PMID: 7787419]
Altiok, S.; Xu, M.; Spiegelman, B.M. PPARgamma induces cell cycle withdrawal: Inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev., 1997, 11(15), 1987-1998.
[] [PMID: 9271121]
Mueller, E.; Sarraf, P.; Tontonoz, P.; Evans, R.M.; Martin, K.J.; Zhang, M.; Fletcher, C.; Singer, S.; Spiegelman, B.M. Terminal differentiation of human breast cancer through PPAR gamma. Mol. Cell, 1998, 1(3), 465-470.
[] [PMID: 9660931]
Demetri, G.D.; Fletcher, C.D.; Mueller, E.; Sarraf, P.; Naujoks, R.; Campbell, N.; Spiegelman, B.M.; Singer, S. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA, 1999, 96(7), 3951-3956.
[] [PMID: 10097144]
Zoete, V.; Grosdidier, A.; Michielin, O. Peroxisome proliferator-activated receptor structures: Ligand specificity, molecular switch and interactions with regulators. Biochim. Biophys. Acta, 2007, 1771(8), 915-925.
[] [PMID: 17317294]
Kliewer, S.A.; Umesono, K.; Mangelsdorf, D.J.; Evans, R.M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature, 1992, 355(6359), 446-449.
[] [PMID: 1310351]
Martin, G.; Schoonjans, K.; Lefebvre, A.M.; Staels, B.; Auwerx, J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J. Biol. Chem., 1997, 272(45), 28210-28217.
[] [PMID: 9353271]
Motojima, K.; Passilly, P.; Peters, J.M.; Gonzalez, F.J.; Latruffe, N. Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner. J. Biol. Chem., 1998, 273(27), 16710-16714.
[] [PMID: 9642225]
Alaynick, W.A. Nuclear receptors, mitochondria and lipid metabolism. Mitochondrion, 2008, 8(4), 329-337.
[] [PMID: 18375192]
Ondrey, F. Peroxisome proliferator-activated receptor gamma pathway targeting in carcinogenesis: Implications for chemoprevention. Clin. Cancer Res., 2009, 15(1), 2-8.
[] [PMID: 19118026]
Blanquicett, C.; Roman, J.; Hart, C.M. Thiazolidinediones as anti-cancer agents. Cancer Ther., 2008, 6(A), 25-34.
Wei, S.; Yang, J.; Lee, S.L.; Kulp, S.K.; Chen, C.S. PPARgamma-independent antitumor effects of thiazolidinediones. Cancer Lett., 2009, 276(2), 119-124.
[] [PMID: 18790559]
Theocharisa, S.; Margeli, A.; Kouraklis, G. Peroxisome proliferator activated receptor-gamma ligands as potent antineoplastic agents. Curr. Med. Chem. Anticancer Agents, 2003, 3(3), 239-251.
[] [PMID: 12769781]
Michalik, L.; Desvergne, B.; Wahli, W. Peroxisome-proliferator-activated receptors and cancers: Complex stories. Nat. Rev. Cancer, 2004, 4(1), 61-70.
[] [PMID: 14708026]
Theocharis, S.; Margeli, A.; Vielh, P.; Kouraklis, G. Peroxisome proliferator-activated receptor-gamma ligands as cell-cycle modulators. Cancer Treat. Rev., 2004, 30(6), 545-554.
[] [PMID: 15325034]
Farce, A.; Renault, N.; Chavatte, P. Structural insight into PPARgamma ligands binding. Curr. Med. Chem., 2009, 16(14), 1768-1789.
[] [PMID: 19442144]
Feige, J.N.; Gelman, L.; Rossi, D.; Zoete, V.; Métivier, R.; Tudor, C.; Anghel, S.I.; Grosdidier, A.; Lathion, C.; Engelborghs, Y.; Michielin, O.; Wahli, W.; Desvergne, B. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J. Biol. Chem., 2007, 282(26), 19152-19166.
[] [PMID: 17468099]
Tolman, K.G. The safety of thiazolidinediones. Expert Opin. Drug Saf., 2011, 10(3), 419-428.
[] [PMID: 21366501]
Davidson, M.B. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence. J. Diabetes Complications, 2016, 30(6), 981-985.
[] [PMID: 27133452]
Hampp, C.; Pippins, J. Pioglitazone and bladder cancer: FDA’s assessment. Pharmacoepidemiol. Drug Saf., 2017, 26(2), 117-118.
[] [PMID: 28067434]
Lincoff, A.M.; Wolski, K.; Nicholls, S.J.; Nissen, S.E. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials. JAMA, 2007, 298(10), 1180-1188.
[] [PMID: 17848652]
Kim, J.; Sato, M.; Choi, J.W.; Kim, H.W.; Yeh, B.I.; Larsen, J.E.; Minna, J.D.; Cha, J.H.; Jeong, Y. Nuclear receptor expression and function in human lung cancer pathogenesis. PLoS One, 2015, 10(8), e0134842
[] [PMID: 26244663]
Elix, C.; Pal, S.K.; Jones, J.O. The role of peroxisome proliferator-activated receptor gamma in prostate cancer. Asian J. Androl., 2018, 20(3), 238-243.
[] [PMID: 28597850]
Mansure, J.J.; Nassim, R.; Kassouf, W. Peroxisome proliferator-activated receptor gamma in bladder cancer: A promising therapeutic target. Cancer Biol. Ther., 2009, 8(7), 6-15.
[] [PMID: 19417560]
Theocharis, S.; Giaginis, C.; Parasi, A.; Margeli, A.; Kakisis, J.; Agapitos, E.; Kouraklis, G. Expression of peroxisome proliferator-activated receptor-gamma in colon cancer: Correlation with histopathological parameters, cell cycle-related molecules, and patients’ survival. Dig. Dis. Sci., 2007, 52(9), 2305-2311.
[] [PMID: 17393321]
Abduljabbar, R.; Al-Kaabi, M.M.; Negm, O.H.; Jerjees, D.; Muftah, A.A.; Mukherjee, A.; Lai, C.F.; Buluwela, L.; Ali, S.; Tighe, P.J.; Green, A.; Ellis, I.; Rakha, E. Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer. Breast Cancer Res. Treat., 2015, 150(3), 511-522.
[] [PMID: 25794775]
Karger, S.; Berger, K.; Eszlinger, M.; Tannapfel, A.; Dralle, H.; Paschke, R.; Führer, D. Evaluation of peroxisome proliferator-activated receptor-gamma expression in benign and malignant thyroid pathologies. Thyroid, 2005, 15(9), 997-1003.
[] [PMID: 16187907]
Gregory Powell, J.; Wang, X.; Allard, B.L.; Sahin, M.; Wang, X.L.; Hay, I.D.; Hiddinga, H.J.; Deshpande, S.S.; Kroll, T.G.; Grebe, S.K.; Eberhardt, N.L.; McIver, B. The PAX8/PPARgamma fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARgamma inhibition. Oncogene, 2004, 23(20), 3634-3641.
[] [PMID: 15077183]
Takahashi, N.; Okumura, T.; Motomura, W.; Fujimoto, Y.; Kawabata, I.; Kohgo, Y. Activation of PPARgamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett., 1999, 455(1-2), 135-139.
[] [PMID: 10428487]
Chang, T.H.; Szabo, E. Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor gamma in non-small cell lung cancer. Cancer Res., 2000, 60(4), 1129-1138.
[PMID: 10706135]
Sarraf, P.; Mueller, E.; Jones, D.; King, F.J.; DeAngelo, D.J.; Partridge, J.B.; Holden, S.A.; Chen, L.B.; Singer, S.; Fletcher, C.; Spiegelman, B.M. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat. Med., 1998, 4(9), 1046-1052.
[] [PMID: 9734398]
Brockman, J.A.; Gupta, R.A.; Dubois, R.N. Activation of PPARgamma leads to inhibition of anchorage-independent growth of human colorectal cancer cells. Gastroenterology, 1998, 115(5), 1049-1055.
[] [PMID: 9797355]
Zhou, J.; Zhang, W.; Liang, B.; Casimiro, M.C.; Whitaker-Menezes, D.; Wang, M.; Lisanti, M.P.; Lanza-Jacoby, S.; Pestell, R.G.; Wang, C. PPARgamma activation induces autophagy in breast cancer cells. Int. J. Biochem. Cell Biol., 2009, 41(11), 2334-2342.
[] [PMID: 19563910]
Soller, M.; Dröse, S.; Brandt, U.; Brüne, B.; von Knethen, A. Mechanism of thiazolidinedione-dependent cell death in Jurkat T cells. Mol. Pharmacol., 2007, 71(6), 1535-1544.
[] [PMID: 17325128]
Kar, R.; Singha, P.K.; Venkatachalam, M.A.; Saikumar, P. A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells. Oncogene, 2009, 28(28), 2556-2568.
[] [PMID: 19448671]
Okura, T.; Nakamura, M.; Takata, Y.; Watanabe, S.; Kitami, Y.; Hiwada, K. Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells. Eur. J. Pharmacol., 2000, 407(3), 227-235.
[] [PMID: 11068018]
Patel, L.; Pass, I.; Coxon, P.; Downes, C.P.; Smith, S.A.; Macphee, C.H. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN. Curr. Biol., 2001, 11(10), 764-768.
[] [PMID: 11378386]
Farrow, B.; Evers, B.M. Activation of PPARgamma increases PTEN expression in pancreatic cancer cells. Biochem. Biophys. Res. Commun., 2003, 301(1), 50-53.
[] [PMID: 12535639]
Han, S.; Roman, J. Rosiglitazone suppresses human lung carcinoma cell growth through PPARgamma-dependent and PPARgamma-independent signal pathways. Mol. Cancer Ther., 2006, 5(2), 430-437.
[] [PMID: 16505118]
Gupta, R.A.; Sarraf, P.; Brockman, J.A.; Shappell, S.B.; Raftery, L.A.; Willson, T.M.; DuBois, R.N. Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J. Biol. Chem., 2003, 278(9), 7431-7438.
[] [PMID: 12468551]
Liu, Y.; Meng, Y.; Li, H.; Li, J.; Fu, J.; Liu, Y.; Chen, X.G. Growth inhibition and differentiation induced by peroxisome proliferator activated receptor gamma ligand rosiglitazone in human melanoma cell line A375. Med. Oncol., 2006, 23(3), 393-402.
[] [PMID: 17018897]
Lovekamp-Swan, T.; Chaffin, C.L. The peroxisome proliferator-activated receptor gamma ligand troglitazone induces apoptosis and p53 in rat granulosa cells. Mol. Cell. Endocrinol., 2005, 233(1-2), 15-24.
[] [PMID: 15767042]
Bonofiglio, D.; Aquila, S.; Catalano, S.; Gabriele, S.; Belmonte, M.; Middea, E.; Qi, H.; Morelli, C.; Gentile, M.; Maggiolini, M.; Andò, S. Peroxisome proliferator-activated receptor-gamma activates p53 gene promoter binding to the nuclear factor-kappaB sequence in human MCF7 breast cancer cells. Mol. Endocrinol., 2006, 20(12), 3083-3092.
[] [PMID: 16887883]
Zand, H.; Rhimipour, A.; Bakhshayesh, M.; Shafiee, M.; Nour Mohammadi, I.; Salimi, S. Involvement of PPAR-gamma and p53 in DHA-induced apoptosis in Reh cells. Mol. Cell. Biochem., 2007, 304(1-2), 71-77.
[] [PMID: 17487454]
Shao, D.; Lazar, M.A. Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation. J. Biol. Chem., 1997, 272(34), 21473-21478.
[] [PMID: 9261165]
Heaney, A.P.; Fernando, M.; Melmed, S. PPAR-gamma receptor ligands: Novel therapy for pituitary adenomas. J. Clin. Invest., 2003, 111(9), 1381-1388.
[] [PMID: 12727930]
Yang, F.G.; Zhang, Z.W.; Xin, D.Q.; Shi, C.J.; Wu, J.P.; Guo, Y.L.; Guan, Y.F. Peroxisome proliferator-activated receptor gamma ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines. Acta Pharmacol. Sin., 2005, 26(6), 753-761.
[] [PMID: 15916743]
Li, M.; Pascual, G.; Glass, C.K. Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene. Mol. Cell. Biol., 2000, 20(13), 4699-4707.
[] [PMID: 10848596]
Piva, R.; Gianferretti, P.; Ciucci, A.; Taulli, R.; Belardo, G.; Santoro, M.G. 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis in human malignant B cells: an effect associated with inhibition of NF-kappa B activity and down-regulation of antiapoptotic proteins. Blood, 2005, 105(4), 1750-1758.
[] [PMID: 15498850]
Kitamura, S.; Miyazaki, Y.; Hiraoka, S.; Nagasawa, Y.; Toyota, M.; Takakura, R.; Kiyohara, T.; Shinomura, Y.; Matsuzawa, Y. PPARgamma agonists inhibit cell growth and suppress the expression of cyclin D1 and EGF-like growth factors in ras-transformed rat intestinal epithelial cells. Int. J. Cancer, 2001, 94(3), 335-342.
[] [PMID: 11745411]
Qin, C.; Burghardt, R.; Smith, R.; Wormke, M.; Stewart, J.; Safe, S. Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells. Cancer Res., 2003, 63(5), 958-964.
[PMID: 12615709]
Morrison, R.F.; Farmer, S.R. Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors, p18(INK4c) and p21(Waf1/Cip1), during adipogenesis. J. Biol. Chem., 1999, 274(24), 17088-17097.
[] [PMID: 10358062]
Elstner, E.; Müller, C.; Koshizuka, K.; Williamson, E.A.; Park, D.; Asou, H.; Shintaku, P.; Said, J.W.; Heber, D.; Koeffler, H.P. Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. USA, 1998, 95(15), 8806-8811.
[] [PMID: 9671760]
Radhakrishnan, S.K.; Gartel, A.L. The PPAR-gamma agonist pioglitazone post-transcriptionally induces p21 in PC3 prostate cancer but not in other cell lines. Cell Cycle, 2005, 4(4), 582-584.
[] [PMID: 15738655]
Toyota, M.; Miyazaki, Y.; Kitamura, S.; Nagasawa, Y.; Kiyohara, T.; Shinomura, Y.; Matsuzawa, Y. Peroxisome proliferator-activated receptor gamma reduces the growth rate of pancreatic cancer cells through the reduction of cyclin D1. Life Sci., 2002, 70(13), 1565-1575.
[] [PMID: 11895107]
Kim, E.J.; Park, K.S.; Chung, S.Y.; Sheen, Y.Y.; Moon, D.C.; Song, Y.S.; Kim, K.S.; Song, S.; Yun, Y.P.; Lee, M.K.; Oh, K.W.; Yoon, D.Y.; Hong, J.T. Peroxisome proliferator-activated receptor-gamma activator 15-deoxy-Delta12,14-prostaglandin J2 inhibits neuroblastoma cell growth through induction of apoptosis: Association with extracellular signal-regulated kinase signal pathway. J. Pharmacol. Exp. Ther., 2003, 307(2), 505-517.
[] [PMID: 12966153]
Chen, G.G.; Lee, J.F.; Wang, S.H.; Chan, U.P.; Ip, P.C.; Lau, W.Y. Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and NF-kappaB in human colon cancer. Life Sci., 2002, 70(22), 2631-2646.
[] [PMID: 12269390]
Shen, Z.N.; Nishida, K.; Doi, H.; Oohashi, T.; Hirohata, S.; Ozaki, T.; Yoshida, A.; Ninomiya, Y.; Inoue, H. Suppression of chondrosarcoma cells by 15-deoxy-Delta 12,14-prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21. Biochem. Biophys. Res. Commun., 2005, 328(2), 375-382.
[] [PMID: 15694358]
Tan, X.W.; Xia, H.; Xu, J.H.; Cao, J.G. Induction of apoptosis in human liver carcinoma HepG2 cell line by 5-allyl-7-gen-difluoromethylenechrysin. World J. Gastroenterol., 2009, 15(18), 2234-2239.
[] [PMID: 19437563]
Zander, T.; Kraus, J.A.; Grommes, C.; Schlegel, U.; Feinstein, D.; Klockgether, T.; Landreth, G.; Koenigsknecht, J.; Heneka, M.T. Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma. J. Neurochem., 2002, 81(5), 1052-1060.
[] [PMID: 12065618]
Kang, D.W.; Choi, C.H.; Park, J.Y.; Kang, S.K.; Kim, Y.K. Ciglitazone induces caspase-independent apoptosis through down-regulation of XIAP and survivin in human glioma cells. Neurochem. Res., 2008, 33(3), 551-561.
[] [PMID: 17940898]
Liu, J.J.; Guo, Y.W.; Fang, Z.G.; Si, X.N.; Wu, X.Y.; Liu, P.Q.; Lin, D.J.; Xiao, R.Z.; Xu, Y.; Wang, C.Z.; Li, X.D.; He, Y.; Huang, R.W. Activation of peroxisome proliferator-activated receptor-gamma induces apoptosis on acute promyelocytic leukemia cells via downregulation of XIAP. Int. J. Mol. Med., 2009, 24(5), 623-632.
[] [PMID: 19787196]
Glass, C.K.; Saijo, K. Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat. Rev. Immunol., 2010, 10(5), 365-376.
[] [PMID: 20414208]
Copland, J.A.; Marlow, L.A.; Kurakata, S.; Fujiwara, K.; Wong, A.K.; Kreinest, P.A.; Williams, S.F.; Haugen, B.R.; Klopper, J.P.; Smallridge, R.C. Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1. Oncogene, 2006, 25(16), 2304-2317.
[] [PMID: 16331265]
Fulzele, S.V.; Chatterjee, A.; Shaik, M.S.; Jackson, T.; Ichite, N.; Singh, M. 15-Deoxy-Delta12,14-prostaglandin J2 enhances docetaxel anti-tumor activity against A549 and H460 non-small-cell lung cancer cell lines and xenograft tumors. Anticancer Drugs, 2007, 18(1), 65-78.
[] [PMID: 17159504]
Palakurthi, S.S.; Aktas, H.; Grubissich, L.M.; Mortensen, R.M.; Halperin, J.A. Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor gamma and mediated by inhibition of translation initiation. Cancer Res., 2001, 61(16), 6213-6218.
[PMID: 11507074]
Abe, A.; Kiriyama, Y.; Hirano, M.; Miura, T.; Kamiya, H.; Harashima, H.; Tokumitsu, Y. Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma. Eur. J. Pharmacol., 2002, 436(1-2), 7-13.
[] [PMID: 11834241]
Smith, U. Pioglitazone: Mechanism of action. Int. J. Clin. Pract. Suppl., 2001, (121), 13-18.
[PMID: 11594239]
Li, X.; Yang, X.; Xu, Y.; Jiang, X.; Li, X.; Nan, F.; Tang, H. Troglitazone inhibits cell proliferation by attenuation of epidermal growth factor receptor signaling independent of peroxisome proliferator-activated receptor gamma. Cell Res., 2009, 19(6), 720-732.
[] [PMID: 19417774]
Rogenhofer, S.; Ellinger, J.; Kahl, P.; Stoehr, C.; Hartmann, A.; Engehausen, D.; Wieland, W.F.; Müller, S.C.; Hofstädter, F.; Walter, B. Enhanced expression of peroxisome proliferate-activated receptor gamma (PPAR-γ) in advanced prostate cancer. Anticancer Res., 2012, 32(8), 3479-3483.
[PMID: 22843934]
Tontonoz, P.; Singer, S.; Forman, B.M.; Sarraf, P.; Fletcher, J.A.; Fletcher, C.D.; Brun, R.P.; Mueller, E.; Altiok, S.; Oppenheim, H.; Evans, R.M.; Spiegelman, B.M. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc. Natl. Acad. Sci. USA, 1997, 94(1), 237-241.
[] [PMID: 8990192]
Debrock, G.; Vanhentenrijk, V.; Sciot, R.; Debiec-Rychter, M.; Oyen, R.; Van Oosterom, A. A phase II trial with rosiglitazone in liposarcoma patients. Br. J. Cancer, 2003, 89(8), 1409-1412.
[] [PMID: 14562008]
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis, 2004, 25(9), 1747-1755.
[] [PMID: 15073042]
Kopelovich, L.; Fay, J.R.; Glazer, R.I.; Crowell, J.A. Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents. Mol. Cancer Ther., 2002, 1(5), 357-363.
[PMID: 12489852]
Han, E.J.; Im, C.N.; Park, S.H.; Moon, E.Y.; Hong, S.H. Combined treatment with peroxisome proliferator-activated receptor (PPAR) gamma ligands and gamma radiation induces apoptosis by PPARγ-independent up-regulation of reactive oxygen species-induced deoxyribonucleic acid damage signals in non-small cell lung cancer cells. Int. J. Radiat. Oncol. Biol. Phys., 2013, 85(5), e239-e248.
[] [PMID: 23332223]
Khoo, N.K.; Hebbar, S.; Zhao, W.; Moore, S.A.; Domann, F.E.; Robbins, M.E. Differential activation of catalase expression and activity by PPAR agonists: implications for astrocyte protection in anti-glioma therapy. Redox Biol., 2013, 1, 70-79.
[] [PMID: 24024139]
Mangoni, M.; Sottili, M.; Gerini, C.; Bonomo, P.; Bottoncetti, A.; Castiglione, F.; Franzese, C.; Cassani, S.; Greto, D.; Masoni, T.; Meattini, I.; Pallotta, S.; Passeri, A.; Pupi, A.; Vanzi, E.; Biti, G.; Livi, L. A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model. Lung Cancer, 2015, 90(3), 405-409.
[] [PMID: 26791799]
Mangoni, M.; Sottili, M.; Gerini, C.; Desideri, I.; Bastida, C.; Pallotta, S.; Castiglione, F.; Bonomo, P.; Meattini, I.; Greto, D.; Cappelli, S.; Di Brina, L.; Loi, M.; Biti, G.; Livi, L. A PPAR-gamma agonist protects from radiation-induced intestinal toxicity. United European Gastroenterol. J., 2017, 5(2), 218-226.
[] [PMID: 28344789]
Mangoni, M.; Sottili, M.; Gerini, C.; Desideri, I.; Bastida, C.; Pallotta, S.; Castiglione, F.; Bonomo, P.; Meattini, I.; Greto, D.; Olmetto, E.; Terziani, F.; Becherini, C.; Delli Paoli, C.; Trombetta, L.; Loi, M.; Biti, G.; Livi, L. A PPAR gamma agonist protects against oral mucositis induced by irradiation in a murine model. Oral Oncol., 2017, 64, 52-58.
[] [PMID: 28024724]
Kaur, S.; Nag, A.; Singh, A.K.; Sharma, K. PPARγ-targeting Potential for Radioprotection. Curr. Drug Targets, 2018, 19(15), 1818-1830.
[] [PMID: 29384061]
Yousefi, B.; Azimi, A.; Majidinia, M.; Shafiei-Irannejad, V.; Badalzadeh, R.; Baradaran, B.; Zarghami, N.; Samadi, N. Balaglitazone reverses P-glycoprotein-mediated multidrug resistance via upregulation of PTEN in a PPARγ-dependent manner in leukemia cells. Tumour Biol., 2017, 39(10), 1010428317716501
[] [PMID: 28978268]
Abbasi, M.M.; Valizadeh, H.; Hamishehkar, H.; Zakeri-Milani, P. Inhibition of P-glycoprotein expression and function by anti-diabetic drugs gliclazide, metformin, and pioglitazone in vitro and in situ. Res. Pharm. Sci., 2016, 11(3), 177-186.
[PMID: 27499787]
Reddy, R.C.; Srirangam, A.; Reddy, K.; Chen, J.; Gangireddy, S.; Kalemkerian, G.P.; Standiford, T.J.; Keshamouni, V.G. Chemotherapeutic drugs induce PPAR-gamma expression and show sequence-specific synergy with PPAR-gamma ligands in inhibition of non-small cell lung cancer. Neoplasia, 2008, 10(6), 597-603.
[] [PMID: 18516296]
Hamaguchi, N.; Hamada, H.; Miyoshi, S.; Irifune, K.; Ito, R.; Miyazaki, T.; Higaki, J. In vitro and in vivo therapeutic efficacy of the PPAR-γ agonist troglitazone in combination with cisplatin against malignant pleural mesothelioma cell growth. Cancer Sci., 2010, 101(9), 1955-1964.
[] [PMID: 20608936]
Girnun, G.D.; Chen, L.; Silvaggi, J.; Drapkin, R.; Chirieac, L.R.; Padera, R.F.; Upadhyay, R.; Vafai, S.B.; Weissleder, R.; Mahmood, U.; Naseri, E.; Buckley, S.; Li, D.; Force, J.; McNamara, K.; Demetri, G.; Spiegelman, B.M.; Wong, K.K. Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin. Clin. Cancer Res., 2008, 14(20), 6478-6486.
[] [PMID: 18927287]
Girnun, G.D.; Naseri, E.; Vafai, S.B.; Qu, L.; Szwaya, J.D.; Bronson, R.; Alberta, J.A.; Spiegelman, B.M. Synergy between PPARgamma ligands and platinum-based drugs in cancer. Cancer Cell, 2007, 11(5), 395-406.
[] [PMID: 17482130]
Tikoo, K.; Kumar, P.; Gupta, J. Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benzaanthracene (DMBA) induced breast cancer rats. BMC Cancer, 2009, 9, 107.
[] [PMID: 19356226]
Lee, S.; Kim, W.; Moon, S.O.; Sung, M.J.; Kim, D.H.; Kang, K.P.; Jang, Y.B.; Lee, J.E.; Jang, K.Y.; Park, S.K. Rosiglitazone ameliorates cisplatin-induced renal injury in mice. Nephrol. Dial. Transplant., 2006, 21(8), 2096-2105.
[] [PMID: 16728429]
Wu, K.; Hu, Y.; Yan, K.; Qi, Y.; Zhang, C.; Zhu, D.; Liu, D.; Zhao, S. microRNA-10b confers cisplatin resistance by activating AKT/mTOR/P70S6K signaling via targeting PPARgamma in esophageal cancer. J. Cell. Physiol., 2019.
[PMID: 31267531]
Akasaki, Y.; Liu, G.; Matundan, H.H.; Ng, H.; Yuan, X.; Zeng, Z.; Black, K.L.; Yu, J.S. A peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and -9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-1B on human glioma cells. J. Biol. Chem., 2006, 281(10), 6165-6174.
[] [PMID: 16319070]
Delgado, J.L.; Hsieh, C.M.; Chan, N.L.; Hiasa, H. Topoisomerases as anticancer targets. Biochem. J., 2018, 475(2), 373-398.
[] [PMID: 29363591]
Kanbe, E.; Abe, A.; Towatari, M.; Kawabe, T.; Saito, H.; Emi, N. DR1-like element in human topoisomerase IIalpha gene involved in enhancement of etoposide-induced apoptosis by PPARgamma ligand. Exp. Hematol., 2003, 31(4), 300-308.
[] [PMID: 12691917]
Gu, C.; Ye, T.; Wells, R.A. Synergistic effects of troglitazone in combination with cytotoxic agents in acute myelogenous leukaemia cells. Leuk. Res., 2006, 30(11), 1447-1451.
[] [PMID: 16704876]
de Sousa Cavalcante, L.; Monteiro, G. Gemcitabine: Metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur. J. Pharmacol., 2014, 741, 8-16.
[] [PMID: 25084222]
Koga, H.; Selvendiran, K.; Sivakumar, R.; Yoshida, T.; Torimura, T.; Ueno, T.; Sata, M. PPARγ potentiates anticancer effects of gemcitabine on human pancreatic cancer cells. Int. J. Oncol., 2012, 40(3), 679-685.
[PMID: 22020928]
Asukai, K.; Kawamoto, K.; Eguchi, H.; Konno, M.; Asai, A.; Iwagami, Y.; Yamada, D.; Asaoka, T.; Noda, T.; Wada, H.; Gotoh, K.; Nishida, N.; Satoh, T.; Doki, Y.; Mori, M.; Ishii, H. Micro-RNA-130a-3p Regulates gemcitabine resistance via pparg in cholangiocarcinoma. Ann. Surg. Oncol., 2017, 24(8), 2344-2352.
[] [PMID: 28560603]
Zhang, Y.; Luo, H.Y.; Liu, G.L.; Wang, D.S.; Wang, Z.Q.; Zeng, Z.L.; Xu, R.H. Prognostic significance and therapeutic implications of peroxisome proliferator-activated receptor γ overexpression in human pancreatic carcinoma. Int. J. Oncol., 2015, 46(1), 175-184.
[] [PMID: 25333644]
Saif, M.W.; Oettle, H.; Vervenne, W.L.; Thomas, J.P.; Spitzer, G.; Visseren-Grul, C.; Enas, N.; Richards, D.A. Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas. Cancer J., 2009, 15(4), 339-343.
[] [PMID: 19672152]
Cao, L.Q.; Wang, X.L.; Wang, Q.; Xue, P.; Jiao, X.Y.; Peng, H.P.; Lu, H.W.; Zheng, Q.; Chen, X.L.; Huang, X.H.; Fu, X.H.; Chen, J.S. Rosiglitazone sensitizes hepatocellular carcinoma cell lines to 5-fluorouracil antitumor activity through activation of the PPARgamma signaling pathway. Acta Pharmacol. Sin., 2009, 30(9), 1316-1322.
[] [PMID: 19684609]
Zhang, Y.Q.; Tang, X.Q.; Sun, L.; Dong, L.; Qin, Y.; Liu, H.Q.; Xia, H.; Cao, J.G. Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating peroxisome proliferator-activated receptor gamma. World J. Gastroenterol., 2007, 13(10), 1534-1540.
[] [PMID: 17461445]
Sottili, M.; Mangoni, M.; Gerini, C.; Salvatore, G.; Castiglione, F.; Desideri, I.; Bonomo, P.; Meattini, I.; Greto, D.; Loi, M.; Francolini, G.; Perna, M.; Grassi, R.; Biti, G.; Livi, L. Peroxisome proliferator activated receptor-gamma stimulation for prevention of 5-fluorouracil-induced oral mucositis in mice. Head Neck, 2018, 40(3), 577-583.
[] [PMID: 29155481]
Papi, A.; Rocchi, P.; Ferreri, A.M.; Guerra, F.; Orlandi, M. Enhanced effects of PPARgamma ligands and RXR selective retinoids in combination to inhibit migration and invasiveness in cancer cells. Oncol. Rep., 2009, 21(4), 1083-1089.
[PMID: 19288012]
Hirase, N.; Yanase, T.; Mu, Y.; Muta, K.; Umemura, T.; Takayanagi, R.; Nawata, H. Thiazolidinedione induces apoptosis and monocytic differentiation in the promyelocytic leukemia cell line HL60. Oncology, 1999, 57(Suppl. 2), 17-26.
[] [PMID: 10545799]
Konopleva, M.; Elstner, E.; McQueen, T.J.; Tsao, T.; Sudarikov, A.; Hu, W.; Schober, W.D.; Wang, R.Y.; Chism, D.; Kornblau, S.M.; Younes, A.; Collins, S.J.; Koeffler, H.P.; Andreeff, M. Peroxisome proliferator-activated receptor gamma and retinoid X receptor ligands are potent inducers of differentiation and apoptosis in leukemias. Mol. Cancer Ther., 2004, 3(10), 1249-1262.
[PMID: 15486192]
Ray, D.M.; Bernstein, S.H.; Phipps, R.P. Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands. Clin. Immunol., 2004, 113(2), 203-213.
[] [PMID: 15451478]
Lee, Y.R.; Yu, H.N.; Noh, E.M.; Kim, J.S.; Song, E.K.; Han, M.K.; Kim, B.S.; Lee, S.H.; Parkd, J. Peroxisome proliferator-activated receptor gamma and retinoic acid receptor synergistically up-regulate the tumor suppressor PTEN in human promyeloid leukemia cells. Int. J. Hematol., 2007, 85(3), 231-237.
Tallman, M.S.; Altman, J.K. How I treat acute promyelocytic leukemia. Blood, 2009, 114(25), 5126-5135.
[] [PMID: 19797519]
Rubin, G.L.; Zhao, Y.; Kalus, A.M.; Simpson, E.R. Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res., 2000, 60(6), 1604-1608.
[PMID: 10749129]
Yang, W.L.; Frucht, H. Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis, 2001, 22(9), 1379-1383.
[] [PMID: 11532858]
Liu, Y.; Zhu, Z.A.; Zhang, S.N.; Mou, J.; Liu, L.; Cui, T.; Pei, D.S. Combinational effect of PPARγ agonist and RXR agonist on the growth of SGC7901 gastric carcinoma cells in vitro. Tumour Biol., 2013, 34(4), 2409-2418.
[] [PMID: 23605322]
Papi, A.; Tatenhorst, L.; Terwel, D.; Hermes, M.; Kummer, M.P.; Orlandi, M.; Heneka, M.T. PPARgamma and RXRgamma ligands act synergistically as potent antineoplastic agents in vitro and in vivo glioma models. J. Neurochem., 2009, 109(6), 1779-1790.
[] [PMID: 19457135]
Desreumaux, P.; Dubuquoy, L.; Nutten, S.; Peuchmaur, M.; Englaro, W.; Schoonjans, K.; Derijard, B.; Desvergne, B.; Wahli, W.; Chambon, P.; Leibowitz, M.D.; Colombel, J.F.; Auwerx, J. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies. J. Exp. Med., 2001, 193(7), 827-838.
[] [PMID: 11283155]
Kocdor, H.; Kocdor, M.A.; Canda, T.; Gurel, D.; Cehreli, R.; Yilmaz, O.; Alakavuklar, M.; Guner, G. Chemopreventive efficacies of rosiglitazone, fenretinide and their combination against rat mammary carcinogenesis. Clin. Transl. Oncol., 2009, 11(4), 243-249.
[] [PMID: 19380302]
Sepmeyer, J.A.; Greer, J.P.; Koyama, T.; Zic, J.A. Open-label pilot study of combination therapy with rosiglitazone and bexarotene in the treatment of cutaneous T-cell lymphoma. J. Am. Acad. Dermatol., 2007, 56(4), 584-587.
[] [PMID: 17184879]
Bonofiglio, D.; Cione, E.; Qi, H.; Pingitore, A.; Perri, M.; Catalano, S.; Vizza, D.; Panno, M.L.; Genchi, G.; Fuqua, S.A.; Andò, S. Combined low doses of PPARgamma and RXR ligands trigger an intrinsic apoptotic pathway in human breast cancer cells. Am. J. Pathol., 2009, 175(3), 1270-1280.
[] [PMID: 19644018]
Demierre, M.F.; Higgins, P.D.; Gruber, S.B.; Hawk, E.; Lippman, S.M. Statins and cancer prevention. Nat. Rev. Cancer, 2005, 5(12), 930-942.
[] [PMID: 16341084]
Kim, W.S.; Kim, M.M.; Choi, H.J.; Yoon, S.S.; Lee, M.H.; Park, K.; Park, C.H.; Kang, W.K. Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Invest. New Drugs, 2001, 19(1), 81-83.
[] [PMID: 11291836]
Lersch, C.; Schmelz, R.; Erdmann, J.; Hollweck, R.; Schulte-Frohlinde, E.; Eckel, F.; Nader, M.; Schusdziarra, V. Treatment of HCC with pravastatin, octreotide, or gemcitabine--a critical evaluation. Hepatogastroenterology, 2004, 51(58), 1099-1103.
[PMID: 15239254]
Knox, J.J.; Siu, L.L.; Chen, E.; Dimitroulakos, J.; Kamel-Reid, S.; Moore, M.J.; Chin, S.; Irish, J.; LaFramboise, S.; Oza, A.M. A Phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervix. Eur. J. Cancer, 2005, 41(4), 523-530.
[] [PMID: 15737556]
Minden, M.D.; Dimitroulakos, J.; Nohynek, D.; Penn, L.Z. Lovastatin induced control of blast cell growth in an elderly patient with acute myeloblastic leukemia. Leuk. Lymphoma, 2001, 40(5-6), 659-662.
[] [PMID: 11426537]
Jakobisiak, M.; Golab, J. Statins can modulate effectiveness of antitumor therapeutic modalities. Med. Res. Rev., 2010, 30(1), 102-135.
[PMID: 19526461]
Xiao, H.; Yang, C.S. Combination regimen with statins and NSAIDs: a promising strategy for cancer chemoprevention. Int. J. Cancer, 2008, 123(5), 983-990.
[] [PMID: 18548583]
Xiao, H.; Zhang, Q.; Lin, Y.; Reddy, B.S.; Yang, C.S. Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int. J. Cancer, 2008, 122(9), 2115-2124.
[] [PMID: 18172863]
Shanafelt, T.D.; Rabe, K.G.; Kay, N.E.; Zent, C.S.; Call, T.G.; Slager, S.L.; Bowen, D.A.; Schwager, S.M.; Nowakowski, G.S. Statin and non-steroidal anti-inflammatory drug use in relation to clinical outcome among patients with Rai stage 0 chronic lymphocytic leukemia. Leuk. Lymphoma, 2010, 51(7), 1233-1240.
[] [PMID: 20496995]
Agarwal, B.; Rao, C.V.; Bhendwal, S.; Ramey, W.R.; Shirin, H.; Reddy, B.S.; Holt, P.R. Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Gastroenterology, 1999, 117(4), 838-847.
[] [PMID: 10500066]
Tapia-Pérez, J.H.; Kirches, E.; Mawrin, C.; Firsching, R.; Schneider, T. Cytotoxic effect of different statins and thiazolidinediones on malignant glioma cells. Cancer Chemother. Pharmacol., 2011, 67(5), 1193-1201.
[] [PMID: 21120479]
Gehring, S.; Tapia-Pérez, J.H.; Kirches, E.; Firsching, R.; Keilhoff, G.; Schneider, T.; Mawrin, C. Cytotoxic effects of statins and thiazolidinediones on meningioma cells. J. Neurooncol., 2011, 102(3), 383-393.
[] [PMID: 20803306]
Yao, C.J.; Lai, G.M.; Chan, C.F.; Cheng, A.L.; Yang, Y.Y.; Chuang, S.E. Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone. Int. J. Cancer, 2006, 118(3), 773-779.
[] [PMID: 16094629]
Lasry, A.; Zinger, A.; Ben-Neriah, Y. Inflammatory networks underlying colorectal cancer. Nat. Immunol., 2016, 17(3), 230-240.
[] [PMID: 26882261]
Umar, A.; Steele, V.E.; Menter, D.G.; Hawk, E.T. Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention. Semin. Oncol., 2016, 43(1), 65-77.
[] [PMID: 26970125]
Nikitakis, N.G.; Hebert, C.; Lopes, M.A.; Reynolds, M.A.; Sauk, J.J. PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells. Int. J. Cancer, 2002, 98(6), 817-823.
[] [PMID: 11948457]
Kohno, H.; Suzuki, R.; Sugie, S.; Tanaka, T. Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands. BMC Cancer, 2005, 5, 46.
[] [PMID: 15892897]
Avis, I.; Martínez, A.; Tauler, J.; Zudaire, E.; Mayburd, A.; Abu-Ghazaleh, R.; Ondrey, F.; Mulshine, J.L. Inhibitors of the arachidonic acid pathway and peroxisome proliferator-activated receptor ligands have superadditive effects on lung cancer growth inhibition. Cancer Res., 2005, 65(10), 4181-4190.
[] [PMID: 15899809]
Coras, B.; Hafner, C.; Reichle, A.; Hohenleutner, U.; Szeimies, R.M.; Landthaler, M.; Vogt, T. Antiangiogenic therapy with pioglitazone, rofecoxib, and trofosfamide in a patient with endemic kaposi sarcoma. Arch. Dermatol., 2004, 140(12), 1504-1507.
[] [PMID: 15611430]
Reichle, A.; Bross, K.; Vogt, T.; Bataille, F.; Wild, P.; Berand, A.; Krause, S.W.; Andreesen, R. Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far-advanced melanoma and soft tissue sarcoma. Cancer, 2004, 101(10), 2247-2256.
[] [PMID: 15470711]
Hau, P.; Kunz-Schughart, L.; Bogdahn, U.; Baumgart, U.; Hirschmann, B.; Weimann, E.; Muhleisen, H.; Ruemmele, P.; Steinbrecher, A.; Reichle, A. Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas - a phase II study. Oncology, 2007, 73(1-2), 21-25.
[] [PMID: 18332649]
Jameera Begam, A.; Jubie, S.; Nanjan, M.J. Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review. Bioorg. Chem., 2017, 71, 257-274.
[] [PMID: 28274582]
Kotta-Loizou, I.; Giaginis, C.; Theocharis, S. The role of peroxisome proliferator-activated receptor-γ in breast cancer. Anticancer. Agents Med. Chem., 2012, 12(9), 1025-1044.
[] [PMID: 22583414]
Papadaki, I.; Mylona, E.; Giannopoulou, I.; Markaki, S.; Keramopoulos, A.; Nakopoulou, L. PPARgamma expression in breast cancer: clinical value and correlation with ERbeta. Histopathology, 2005, 46(1), 37-42.
[] [PMID: 15656884]
Yu, H.N.; Noh, E.M.; Lee, Y.R.; Roh, S.G.; Song, E.K.; Han, M.K.; Lee, Y.C.; Shim, I.K.; Lee, S.J.; Jung, S.H.; Kim, J.S.; Youn, H.J. Troglitazone enhances tamoxifen-induced growth inhibitory activity of MCF-7 cells. Biochem. Biophys. Res. Commun., 2008, 377(1), 242-247.
[] [PMID: 18835379]
Shiau, C.W.; Yang, C.C.; Kulp, S.K.; Chen, K.F.; Chen, C.S.; Huang, J.W.; Chen, C.S. Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma. Cancer Res., 2005, 65(4), 1561-1569.
[] [PMID: 15735046]
Li, X.; He, J.; Li, B.; Gao, M.; Zeng, Y.; Lian, J.; Shi, C.; Huang, Y.; He, F. The PPARγ agonist rosiglitazone sensitizes the BH3 mimetic (-)-gossypol to induce apoptosis in cancer cells with high level of Bcl-2. Mol. Carcinog., 2018, 57(9), 1213-1222.
[] [PMID: 29856104]
Manasanch, E.E.; Orlowski, R.Z. Proteasome inhibitors in cancer therapy. Nat. Rev. Clin. Oncol., 2017, 14(7), 417-433.
[] [PMID: 28117417]
von Schwarzenberg, K.; Held, S.A.; Schaub, A.; Brauer, K.M.; Bringmann, A.; Brossart, P. Proteasome inhibition overcomes the resistance of renal cell carcinoma cells against the PPARgamma ligand troglitazone. Cell. Mol. Life Sci., 2009, 66(7), 1295-1308.
[] [PMID: 19252820]
Freudlsperger, C.; Thies, A.; Pfüller, U.; Schumacher, U. The proteasome inhibitor bortezomib augments anti-proliferative effects of mistletoe lectin-I and the PPAR-gamma agonist rosiglitazone in human melanoma cells. Anticancer Res., 2007, 27(1A), 207-213.
[PMID: 17352234]
Raught, B.; Gingras, A.C.; Sonenberg, N. The target of rapamycin (TOR) proteins. Proc. Natl. Acad. Sci. USA, 2001, 98(13), 7037-7044.
[] [PMID: 11416184]
Li, Y.; Seto, E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb. Perspect. Med., 2016, 6(10), a026831
[] [PMID: 27599530]
Heers, H.; Stanislaw, J.; Harrelson, J.; Lee, M.W. Valproic acid as an adjunctive therapeutic agent for the treatment of breast cancer. Eur. J. Pharmacol., 2018, 835, 61-74.
[] [PMID: 30075223]
Annicotte, J.S.; Iankova, I.; Miard, S.; Fritz, V.; Sarruf, D.; Abella, A.; Berthe, M.L.; Noël, D.; Pillon, A.; Iborra, F.; Dubus, P.; Maudelonde, T.; Culine, S.; Fajas, L. Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer. Mol. Cell. Biol., 2006, 26(20), 7561-7574.
[] [PMID: 17015477]
Aouali, N.; Palissot, V.; El-Khoury, V.; Moussay, E.; Janji, B.; Pierson, S.; Brons, N.H.; Kellner, L.; Bosseler, M.; Van Moer, K.; Berchem, G. Peroxisome proliferator-activated receptor gamma agonists potentiate the cytotoxic effect of valproic acid in multiple myeloma cells. Br. J. Haematol., 2009, 147(5), 662-671.
[] [PMID: 19793255]
Chang, T.H.; Szabo, E. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin. Cancer Res., 2002, 8(4), 1206-1212.
[PMID: 11948134]
Zang, C.; Liu, H.; Waechter, M.; Eucker, J.; Bertz, J.; Possinger, K.; Koeffler, H.P.; Elstner, E. Dual PPARalpha/gamma ligand TZD18 either alone or in combination with imatinib inhibits proliferation and induces apoptosis of human CML cell lines. Cell Cycle, 2006, 5(19), 2237-2243.
[] [PMID: 17102607]
Liu, H.; Zang, C.; Fenner, M.H.; Liu, D.; Possinger, K.; Koeffler, H.P.; Elstner, E. Growth inhibition and apoptosis in human Philadelphia chromosome-positive lymphoblastic leukemia cell lines by treatment with the dual PPARalpha/gamma ligand TZD18. Blood, 2006, 107(9), 3683-3692.
[] [PMID: 16403907]
Bertz, J.; Zang, C.; Liu, H.; Wächter, M.; Possinger, K.; Koeffler, H.P.; Elstner, E. Compound 48, a novel dual PPAR alpha/gamma ligand, inhibits the growth of human CML cell lines and enhances the anticancer-effects of imatinib. Leuk. Res., 2009, 33(5), 686-692.
[] [PMID: 19131110]
Prost, S.; Relouzat, F.; Spentchian, M.; Ouzegdouh, Y.; Saliba, J.; Massonnet, G.; Beressi, J.P.; Verhoeyen, E.; Raggueneau, V.; Maneglier, B.; Castaigne, S.; Chomienne, C.; Chrétien, S.; Rousselot, P.; Leboulch, P. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature, 2015, 525(7569), 380-383.
[] [PMID: 26331539]
Glodkowska-Mrowka, E.; Manda-Handzlik, A.; Stelmaszczyk-Emmel, A.; Seferynska, I.; Stoklosa, T.; Przybylski, J.; Mrowka, P. PPARγ ligands increase antileukemic activity of second- and thirdgeneration tyrosine kinase inhibitors in chronic myeloid leukemia cells. Blood Cancer J., 2016, 6e377.
[] [PMID: 26745851]
Rousselot, P.; Prost, S.; Guilhot, J.; Roy, L.; Etienne, G.; Legros, L.; Charbonnier, A.; Coiteux, V.; Cony-Makhoul, P.; Huguet, F.; Cayssials, E.; Cayuela, J.M.; Relouzat, F.; Delord, M.; Bruzzoni-Giovanelli, H.; Morisset, L.; Mahon, F.X.; Guilhot, F.; Leboulch, P.; French, C.M.L.G. French CML Group. Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study. Cancer, 2017, 123(10), 1791-1799.
[] [PMID: 28026860]
Wang, J.; Lu, L.; Kok, C.H.; Saunders, V.A.; Goyne, J.M.; Dang, P.; Leclercq, T.M.; Hughes, T.P.; White, D.L. Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells. Haematologica, 2017, 102(5), 843-853.
[] [PMID: 28154092]
Lee, S.Y.; Hur, G.Y.; Jung, K.H.; Jung, H.C.; Lee, S.Y.; Kim, J.H.; Shin, C.; Shim, J.J. In, K.H.; Kang, K.H.; Yoo, S.H. PPAR-gamma agonist increase gefitinib’s antitumor activity through PTEN expression. Lung Cancer, 2006, 51(3), 297-301.
[] [PMID: 16386327]
Park, B.H.; Lee, S.B.; Stolz, D.B.; Lee, Y.J.; Lee, B.C. Synergistic interactions between heregulin and peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist in breast cancer cells. J. Biol. Chem., 2011, 286(22), 20087-20099.
[] [PMID: 21467033]
Manabe, A.; Furukawa, C.; Hasegawa, H.; Matsunaga, T.; Endo, S.; Ikari, A. Upregulation of transient receptor potential melastatin 6 channel expression by rosiglitazone and all-trans-retinoic acid in erlotinib-treated renal tubular epithelial cells. J. Cell. Physiol., 2019, 234(6), 8951-8962.
[] [PMID: 30461012]
Chandra, M.; Miriyala, S.; Panchatcharam, M. PPARγ and its role in cardiovascular diseases. PPAR Res., 2017., 20176404638
[] [PMID: 28243251]
Lee, K.S.; Park, S.J.; Hwang, P.H.; Yi, H.K.; Song, C.H.; Chai, O.H.; Kim, J.S.; Lee, M.K.; Lee, Y.C. PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J., 2005, 19(8), 1033-1035.
[] [PMID: 15788448]
Corona, J.C.; Duchen, M.R. PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease. Free Radic. Biol. Med., 2016, 100, 153-163.
[] [PMID: 27352979]
Dantas, A.T.; Pereira, M.C.; de Melo Rego, M.J.; da Rocha, L.F., Jr Pitta, Ida.R.; Marques, C.D.; Duarte, A.L.; Pitta, M.G. The role of PPAR Gamma in systemic sclerosis. PPAR Res., 2015., 2015124624
[] [PMID: 26064084]
Clark, R.B.; Bishop-Bailey, D.; Estrada-Hernandez, T.; Hla, T.; Puddington, L.; Padula, S.J. The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J. Immunol., 2000, 164(3), 1364-1371.
[] [PMID: 10640751]
Ricote, M.; Li, A.C.; Willson, T.M.; Kelly, C.J.; Glass, C.K. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature, 1998, 391(6662), 79-82.
[] [PMID: 9422508]
Padilla, J.; Leung, E.; Phipps, R.P. Human B lymphocytes and B lymphomas express PPAR-gamma and are killed by PPAR-gamma agonists. Clin. Immunol., 2002, 103(1), 22-33.
[] [PMID: 11987982]
Korpal, M.; Puyang, X.; Jeremy Wu, Z.; Seiler, R.; Furman, C.; Oo, H.Z.; Seiler, M.; Irwin, S.; Subramanian, V.; Julie Joshi, J.; Wang, C.K.; Rimkunas, V.; Tortora, D.; Yang, H.; Kumar, N.; Kuznetsov, G.; Matijevic, M.; Chow, J.; Kumar, P.; Zou, J.; Feala, J.; Corson, L.; Henry, R.; Selvaraj, A.; Davis, A.; Bloudoff, K.; Douglas, J.; Kiss, B.; Roberts, M.; Fazli, L.; Black, P.C.; Fekkes, P.; Smith, P.G.; Warmuth, M.; Yu, L.; Hao, M.H.; Larsen, N.; Daugaard, M.; Zhu, P. Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer. Nat. Commun., 2017, 8(1), 103.
[] [PMID: 28740126]
Nobs, S.P.; Natali, S.; Pohlmeier, L.; Okreglicka, K.; Schneider, C.; Kurrer, M.; Sallusto, F.; Kopf, M. PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation. J. Exp. Med., 2017, 214(10), 3015-3035.
[] [PMID: 28798029]
Santha, S.; Viswakarma, N.; Das, S.; Rana, A.; Rana, B. Tumor Necrosis Factor-related Apoptosis-inducing ligand (TRAIL)-troglitazone-induced apoptosis in prostate cancer cells involve amp-activated protein kinase. J. Biol. Chem., 2015, 290(36), 21865-21875.
[] [PMID: 26198640]
Santha, S.; Davaakhuu, G.; Basu, A.; Ke, R.; Das, S.; Rana, A.; Rana, B. Modulation of glycogen synthase kinase-3β following TRAIL combinatorial treatment in cancer cells. Oncotarget, 2016, 7(41), 66892-66905.
[] [PMID: 27602497]
Plissonnier, M.L.; Fauconnet, S.; Bittard, H.; Lascombe, I. The antidiabetic drug ciglitazone induces high grade bladder cancer cells apoptosis through the up-regulation of TRAIL. PLoS One, 2011, 6(12), e28354
[] [PMID: 22174792]
Plissonnier, M.L.; Fauconnet, S.; Bittard, H.; Mougin, C.; Rommelaere, J.; Lascombe, I. Cell death and restoration of TRAIL-sensitivity by ciglitazone in resistant cervical cancer cells. Oncotarget, 2017, 8(64), 107744-107762.
[] [PMID: 29296202]
Nazim, U.M.; Moon, J.H.; Lee, Y.J.; Seol, J.W.; Park, S.Y. PPARγ activation by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux. Oncotarget, 2017, 8(16), 26819-26831.
[] [PMID: 28460464]
Dicitore, A.; Caraglia, M.; Gaudenzi, G.; Manfredi, G.; Amato, B.; Mari, D.; Persani, L.; Arra, C.; Vitale, G. Type I interferon-mediated pathway interacts with peroxisome proliferator activated receptor-γ (PPAR-γ): At the cross-road of pancreatic cancer cell proliferation. Biochim. Biophys. Acta, 2014, 1845(1), 42-52.
[PMID: 24295567]
Vitale, G.; Zappavigna, S.; Marra, M.; Dicitore, A.; Meschini, S.; Condello, M.; Arancia, G.; Castiglioni, S.; Maroni, P.; Bendinelli, P.; Piccoletti, R.; van Koetsveld, P.M.; Cavagnini, F.; Budillon, A.; Abbruzzese, A.; Hofland, L.J.; Caraglia, M. The PPAR-γ agonist troglitazone antagonizes survival pathways induced by STAT-3 in recombinant interferon-β treated pancreatic cancer cells. Biotechnol. Adv., 2012, 30(1), 169-184.
[] [PMID: 21871555]
Goyal, G.; Wong, K.; Nirschl, C.J.; Souders, N.; Neuberg, D.; Anandasabapathy, N.; Dranoff, G. PPARγ contributes to immunity induced by cancer cell vaccines that secrete GM-CSF. Cancer Immunol. Res., 2018, 6(6), 723-732.
[] [PMID: 29669721]
Yang, Z.; Bagheri-Yarmand, R.; Balasenthil, S.; Hortobagyi, G.; Sahin, A.A.; Barnes, C.J.; Kumar, R. HER2 regulation of peroxisome proliferator-activated receptor gamma (PPARgamma) expression and sensitivity of breast cancer cells to PPARgamma ligand therapy. Clin. Cancer Res., 2003, 9(8), 3198-3203.
[PMID: 12912973]
Pal, T.; Joshi, H.; Ramaa, C.S. Design and development of oxazol-5-ones as potential partial PPAR-γ agonist against cancer cell lines. Anticancer. Agents Med. Chem., 2014, 14(6), 872-883.
[] [PMID: 24875128]
Joshi, H.; Pal, T.; Ramaa, C.S. A new dawn for the use of thiazolidinediones in cancer therapy. Expert Opin. Investig. Drugs, 2014, 23(4), 501-510.
[] [PMID: 24597633]
Yamamoto, Y.; Fujita, M.; Koma, H.; Yamamori, M.; Nakamura, T.; Okamura, N.; Yagami, T. 15-Deoxy-Δ12,14-prostaglandin J2 enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPARγ pathways. Biochem. Biophys. Res. Commun., 2011, 410(3), 563-567.
[] [PMID: 21683069]
Haydon, R.C.; Luu, H.H.; He, T.C. Osteosarcoma and osteoblastic differentiation: A new perspective on oncogenesis. Clin. Orthop. Relat. Res., 2007, 454(454), 237-246.
[] [PMID: 17075380]
Mrówka, P.; Glodkowska, E.; Nowis, D.; Legat, M.; Issat, T.; Makowski, M.; Szokalska, A.; Janowska, S.; Stoklosa, T.; Jakóbisiak, M.; Golab, J. Ciglitazone, an agonist of peroxisome proliferator-activated receptor gamma, exerts potentiated cytostatic/cytotoxic effects against tumor cells when combined with lovastatin. Int. J. Oncol., 2008, 32(1), 249-255.
[PMID: 18097565]
Kim, B.M.; Maeng, K.; Lee, K.H.; Hong, S.H. Combined treatment with the Cox-2 inhibitor niflumic acid and PPARγ ligand ciglitazone induces ER stress/caspase-8-mediated apoptosis in human lung cancer cells. Cancer Lett., 2011, 300(2), 134-144.
[] [PMID: 21067863]
Yokoyama, Y.; Xin, B.; Shigeto, T.; Mizunuma, H. Combination of ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, and cisplatin enhances the inhibition of growth of human ovarian cancers. J. Cancer Res. Clin. Oncol., 2011, 137(8), 1219-1228.
[] [PMID: 21681689]
Bräutigam, K.; Biernath-Wüpping, J.; Bauerschlag, D.O.; von Kaisenberg, C.S.; Jonat, W.; Maass, N.; Arnold, N.; Meinhold-Heerlein, I. Combined treatment with TRAIL and PPARγ ligands overcomes chemoresistance of ovarian cancer cell lines. J. Cancer Res. Clin. Oncol., 2011, 137(5), 875-886.
[] [PMID: 20878528]
Huang, H.; Wu, D.; Fu, J.; Chen, G.; Chang, W.; Chow, H.C.; Leung, A.Y.; Liang, R. All-trans retinoic acid can intensify the growth inhibition and differentiation induction effect of rosiglitazone on multiple myeloma cells. Eur. J. Haematol., 2009, 83(3), 191-202.
[] [PMID: 19467017]
Cesario, R.M.; Stone, J.; Yen, W.C.; Bissonnette, R.P.; Lamph, W.W. Differentiation and growth inhibition mediated via the RXR: PPARgamma heterodimer in colon cancer. Cancer Lett., 2006, 240(2), 225-233.
[] [PMID: 16271436]
Mansour, M.; Schwartz, D.; Judd, R.; Akingbemi, B.; Braden, T.; Morrison, E.; Dennis, J.; Bartol, F.; Hazi, A.; Napier, I.; Abdel-Mageed, A.B. Thiazolidinediones/PPARγ agonists and fatty acid synthase inhibitors as an experimental combination therapy for prostate cancer. Int. J. Oncol., 2011, 38(2), 537-546.
[] [PMID: 21170507]
Fu, H.; Zhang, J.; Pan, J.; Zhang, Q.; Lu, Y.; Wen, W.; Lubet, R.A.; Szabo, E.; Chen, R.; Wang, Y.; Chen, D.R.; You, M. Chemoprevention of lung carcinogenesis by the combination of aerosolized budesonide and oral pioglitazone in A/J mice. Mol. Carcinog., 2011, 50(12), 913-921.
[] [PMID: 21374736]
Gottfried, E.; Rogenhofer, S.; Waibel, H.; Kunz-Schughart, L.A.; Reichle, A.; Wehrstein, M.; Peuker, A.; Peter, K.; Hartmannsgruber, G.; Andreesen, R.; Kreutz, M. Pioglitazone modulates tumor cell metabolism and proliferation in multicellular tumor spheroids. Cancer Chemother. Pharmacol., 2011, 67(1), 117-126.
[] [PMID: 20217088]
An, Z.; Liu, X.; Song, H.; Choi, C.; Kim, W.D.; Yu, J.R.; Park, W.Y. Effect of troglitazone on radiation sensitivity in cervix cancer cells. Radiat. Oncol. J., 2012, 30(2), 78-87.
[] [PMID: 22984686]
Yan, K.H.; Yao, C.J.; Chang, H.Y.; Lai, G.M.; Cheng, A.L.; Chuang, S.E. The synergistic anticancer effect of troglitazone combined with aspirin causes cell cycle arrest and apoptosis in human lung cancer cells. Mol. Carcinog., 2010, 49(3), 235-246.
[PMID: 19908241]

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