Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Molecular Mechanisms of the Action of Myricetin in Cancer

Author(s): Yutao Xie, Yunlong Wang*, Wei Xiang, Qiaoying Wang and Yajun Cao

Volume 20, Issue 2, 2020

Page: [123 - 133] Pages: 11

DOI: 10.2174/1389557519666191018112756

Price: $65

conference banner
Abstract

Natural compounds, such as paclitaxel and camptothecin, have great effects on the treatment of tumors. Such natural chemicals often achieve anti-tumor effects through a variety of mechanisms. Therefore, it is of great significance to conduct further studies on the anticancer mechanism of natural anticancer agents to lay a solid foundation for the development of new drugs. Myricetin, originally isolated from Myrica nagi, is a natural pigment of flavonoids that can inhibit the growth of cancer cells (such as liver cancer, rectal cancer, skin cancer and lung cancer, etc.). It can regulate many intracellular activities (such as anti-inflammatory and blood lipids regulation) and can even be bacteriostatic. The purpose of this paper is to outline the molecular pathways of the anticancer effects of myricetin, including the effect on cancer cell death, proliferation, angiogenesis, metastasis and cell signaling pathway.

Keywords: Myricetin, cancer, anticancer, molecular mechanism, natural, proliferation, angiogenesis.

Graphical Abstract
[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull., 2017, 7(3), 339-348.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[3]
Griffiths, L.A.; Smith, G.E. Metabolism of myricetin and related compounds in the rat: Metabolite formation in vivo and by the intestinal microflora in vitro. Biochem. J., 1972, 130(1), 141-151.
[http://dx.doi.org/10.1042/bj1300141] [PMID: 4655415]
[4]
Hui, C.; Qi, X.; Qianyong, Z.; Xiaoli, P.; Jundong, Z.; Mantian, M. Flavonoids, flavonoid subclasses and breast cancer risk: A meta-analysis of epidemiologic studies. PLoS One, 2013, 8(1)e54318
[http://dx.doi.org/10.1371/journal.pone.0054318] [PMID: 23349849]
[5]
Seydi, E.; Rasekh, H.R.; Salimi, A.; Mohsenifar, Z.; Pourahmad, J. Myricetin selectively induces apoptosis on cancerous hepatocytes by directly targeting their mitochondria. Basic Clin. Pharmacol. Toxicol., 2016, 119(3), 249-258.
[http://dx.doi.org/10.1111/bcpt.12572] [PMID: 26919160]
[6]
Rathmell, J.C.; Thompson, C.B. Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell, 2002, 109(Suppl. 1), S97-S107.
[http://dx.doi.org/10.1016/S0092-8674(02)00704-3] [PMID: 11983156]
[7]
Peter, M.E. Programmed cell death: Apoptosis meets necrosis. Nature, 2011, 471(7338), 310-312.
[http://dx.doi.org/10.1038/471310a] [PMID: 21412328]
[8]
Chung, C. Restoring the switch for cancer cell death: Targeting the apoptosis signaling pathway. Am. J. Health Syst. Pharm., 2018, 75(13), 945-952.
[http://dx.doi.org/10.2146/ajhp170607] [PMID: 29759975]
[9]
Fujita, K.; Iwama, H.; Oura, K.; Tadokoro, T.; Samukawa, E.; Sakamoto, T.; Nomura, T.; Tani, J.; Yoneyama, H.; Morishita, A.; Himoto, T.; Hirashima, M.; Masaki, T. Cancer therapy due to apoptosis: Galectin-9. Int. J. Mol. Sci., 2017, 18(1)E74
[http://dx.doi.org/10.3390/ijms18010074] [PMID: 28045432]
[10]
Campbell, K.J.; Tait, S.W.G. Targeting BCL-2 regulated apoptosis in cancer. Open Biol., 2018, 8(5)180002
[http://dx.doi.org/10.1098/rsob.180002] [PMID: 29769323]
[11]
Ye, C.; Zhang, C.; Huang, H.; Yang, B.; Xiao, G.; Kong, D.; Tian, Q.; Song, Q.; Song, Y.; Tan, H.; Wang, Y.; Zhou, T.; Zi, X.; Sun, Y. The natural compound myricetin effectively represses the malignant progression of prostate cancer by inhibiting PIM1 and disrupting the PIM1/CXCR4 interaction. Cell. Physiol. Biochem., 2018, 48(3), 1230-1244.
[http://dx.doi.org/10.1159/000492009] [PMID: 30045021]
[12]
Knickle, A.; Fernando, W.; Greenshields, A.L.; Rupasinghe, H.P.V.; Hoskin, D.W. Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide. Food Chem. Toxicol., 2018, 118, 154-167.
[http://dx.doi.org/10.1016/j.fct.2018.05.005]
[13]
Ci, Y.; Zhang, Y.; Liu, Y.; Lu, S.; Cao, J.; Li, H.; Zhang, J.; Huang, Z.; Zhu, X.; Gao, J.; Han, M. Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9. Phytother. Res., 2018, 32(7), 1373-1381.
[http://dx.doi.org/10.1002/ptr.6071] [PMID: 29532526]
[14]
Jiao, D.; Zhang, X.D. Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway. Oncol. Rep., 2016, 36(1), 342-348.
[http://dx.doi.org/10.3892/or.2016.4777] [PMID: 27122002]
[15]
Lee, J.H.; Choi, Y.J.; Park, S.-H. Potential role of nucleoside diphosphate kinase in myricetin-induced selective apoptosis in colon cancer hct-15 cells. Food Chem. Toxicol, 2018, 116(Part B), 315-322.
[16]
Kim, M.E.; Ha, T.K.; Yoon, J.H.; Lee, J.S. Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway. Anticancer Res., 2014, 34(2), 701-706.
[PMID: 24511002]
[17]
Zhao, H.F.; Wang, G.; Wu, C.P.; Zhou, X.M.; Wang, J.; Chen, Z.P.; To, S.T.; Li, W.P. A multi-targeted natural flavonoid myricetin suppresses lamellipodia and focal adhesions formation and impedes glioblastoma cell invasiveness and abnormal motility. CNS Neurol. Disord. Drug Targets, 2018, 17(7), 557-567.
[http://dx.doi.org/10.2174/1871527317666180611090006] [PMID: 29886836]
[18]
Zheng, A.W.; Chen, Y.Q.; Zhao, L.Q.; Feng, J.G. Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells. Oncol. Lett., 2017, 13(6), 4974-4978.
[http://dx.doi.org/10.3892/ol.2017.6031] [PMID: 28588737]
[19]
Xu, Y.; Xie, Q.; Wu, S.; Yi, D.; Yu, Y.; Liu, S.; Li, S.; Li, Z. Myricetin induces apoptosis via endoplasmic reticulum stress and DNA double-strand breaks in human ovarian cancer cells. Mol. Med. Rep., 2016, 13(3), 2094-2100.
[http://dx.doi.org/10.3892/mmr.2016.4763] [PMID: 26782830]
[20]
Ha, T.K.; Jung, I.; Kim, M.E.; Bae, S.K.; Lee, J.S. Anti-cancer activity of myricetin against human papillary thyroid cancer cells involves mitochondrial dysfunction-mediated apoptosis. Biomed. Pharmacother., 2017, 91, 378-384.
[http://dx.doi.org/10.1016/j.biopha.2017.04.100] [PMID: 28463801]
[21]
Jo, S.; Ha, T.K.; Han, S-H.; Kim, M.E.; Jung, I.; Lee, H.W.; Bae, S.K.; Lee, J.S. Myricetin induces apoptosis of human anaplastic thyroid cancer cells via mitochondria dysfunction. Anticancer Res., 2017, 37(4), 1705-1710.
[http://dx.doi.org/10.21873/anticanres.11502] [PMID: 28373432]
[22]
Iyer, S.C.; Gopal, A.; Halagowder, D. Myricetin induces apoptosis by inhibiting P21 activated kinase 1 (PAK1) signaling cascade in hepatocellular carcinoma. Mol. Cell. Biochem., 2015, 407(1-2), 223-237.
[http://dx.doi.org/10.1007/s11010-015-2471-6] [PMID: 26104578]
[23]
Feng, J.; Chen, X.; Wang, Y.; Du, Y.; Sun, Q.; Zang, W.; Zhao, G. Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells. Mol. Cell. Biochem., 2015, 408(1-2), 163-170.
[http://dx.doi.org/10.1007/s11010-015-2492-1] [PMID: 26112905]
[24]
Yi, J.L.; Shi, S.; Shen, Y.L.; Wang, L.; Chen, H.Y.; Zhu, J.; Ding, Y. Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines. Int. J. Clin. Exp. Pathol., 2015, 8(2), 1116-1127.
[PMID: 25972998]
[25]
Zhang, S.; Wang, L.; Liu, H.; Zhao, G.; Ming, L. Enhancement of recombinant myricetin on the radiosensitivity of lung cancer A549 and H1299 cells. Diagn. Pathol., 2014, 9, 68.
[http://dx.doi.org/10.1186/1746-1596-9-68] [PMID: 24650056]
[26]
Wang, L.; Feng, J.; Chen, X.; Guo, W.; Du, Y.; Wang, Y.; Zang, W.; Zhang, S.; Zhao, G. Myricetin enhance chemosensitivity of 5-fluorouracil on esophageal carcinoma in vitro and in vivo. Cancer Cell Int., 2014, 14, 71.
[http://dx.doi.org/10.1186/s12935-014-0071-2] [PMID: 25788859]
[27]
Sun, F.; Zheng, X.Y.; Ye, J.; Wu, T.T.; Wang, Jl.; Chen, W. Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo. Nutr. Cancer, 2012, 64(4), 599-606.
[http://dx.doi.org/10.1080/01635581.2012.665564] [PMID: 22482362]
[28]
Phillips, P.A.; Sangwan, V.; Borja-Cacho, D.; Dudeja, V.; Vickers, S.M.; Saluja, A.K. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett., 2011, 308(2), 181-188.
[http://dx.doi.org/10.1016/j.canlet.2011.05.002] [PMID: 21676539]
[29]
Jung, S.K.; Lee, K.W.; Byun, S.; Kang, N.J.; Lim, S.H.; Heo, Y-S.; Bode, A.M.; Bowden, G.T.; Lee, H.J.; Dong, Z. Myricetin suppresses UVB-induced skin cancer by targeting Fyn. Cancer Res., 2008, 68(14), 6021-6029.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0899] [PMID: 18632659]
[30]
Maggioni, D.; Nicolini, G.; Rigolio, R.; Biffi, L.; Pignataro, L.; Gaini, R.; Garavello, W. Myricetin and naringenin inhibit human squamous cell carcinoma proliferation and migration in vitro. Nutr. Cancer, 2014, 66(7), 1257-1267.
[http://dx.doi.org/10.1080/01635581.2014.951732] [PMID: 25256786]
[31]
Zhang, X.H.; Chen, S.Y.; Tang, L.; Shen, Y.Z.; Luo, L.; Xu, C.W.; Liu, Q.; Li, D. Myricetin induces apoptosis in HepG2 cells through Akt/p70S6K/bad signaling and mitochondrial apoptotic pathway. Anticancer. Agents Med. Chem., 2013, 13(10), 1575-1581.
[http://dx.doi.org/10.2174/1871520613666131125123059] [PMID: 23438827]
[32]
Brown, K.K.; Toker, A. The phosphoinositide 3-kinase pathway and therapy resistance in cancer. F1000Prime Rep., 2015, 7(2), 13.
[http://dx.doi.org/10.12703/P7-13] [PMID: 25750731]
[33]
Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug Discov., 2009, 8(8), 627-644.
[http://dx.doi.org/10.1038/nrd2926] [PMID: 19644473]
[34]
Yamamoto, T.; Kambe, F.; Cao, X.; Lu, X.; Ishiguro, N.; Seo, H. Parathyroid hormone activates phosphoinositide 3-kinase-Akt-Bad cascade in osteoblast-like cells. Bone, 2007, 40(2), 354-359.
[http://dx.doi.org/10.1016/j.bone.2006.09.002] [PMID: 17046344]
[35]
Blalock, W.L.; Navolanic, P.M.; Steelman, L.S.; Shelton, J.G.; Moye, P.W.; Lee, J.T.; Franklin, R.A.; Mirza, A.; McMahon, M.; White, M.K.; McCubrey, J.A. Requirement for the PI3K/Akt pathway in MEK1-mediated growth and prevention of apoptosis: Identification of an Achilles heel in leukemia. Leukemia, 2003, 17(6), 1058-1067.
[http://dx.doi.org/10.1038/sj.leu.2402925] [PMID: 12764369]
[36]
Morales, P.; Haza, A.I. Selective apoptotic effects of piceatannol and myricetin in human cancer cells. J. Appl. Toxicol., 2012, 32(12), 986-993.
[http://dx.doi.org/10.1002/jat.1725] [PMID: 21935971]
[37]
Huang, H.; Chen, A.Y.; Ye, X.; Li, B.; Rojanasakul, Y.; Rankin, G.O.; Chen, Y.C. Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway. Int. J. Oncol., 2015, 47(4), 1494-1502.
[http://dx.doi.org/10.3892/ijo.2015.3133] [PMID: 26315556]
[38]
Zhang, Y.; Chen, S.; Wei, C.; Rankin, G.O.; Ye, X.; Chen, Y.C. Flavonoids from Chinese bayberry leaves induced apoptosis and G1 cell cycle arrest via Erk pathway in ovarian cancer cells. Eur. J. Med. Chem., 2018, 147, 218-226.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.084] [PMID: 29438890]
[39]
Yang, Y.; Dong, F.; Liu, X.; Xu, J.; Wu, X.; Liu, W.; Zheng, Y. Crosstalk of oxidative damage, apoptosis, and autophagy under endoplasmic reticulum (ER) stress involved in thifluzamide-induced liver damage in zebrafish (danio rerio). Environ. Pollut., 2018, 143(Pt B), 1904-1911.
[40]
Lai, X.Y.; Egan, L.J. Suppression of radiation-induced DNA double- strand break repair by MyD88 is accompanied by apoptosis and crypt loss in mouse colon. Oncogenesis, 2013
[http://dx.doi.org/10.1038/oncsis.2013.22] [PMID: 23939014]
[41]
Hagiwara, Y.; Niimi, A.; Isono, M.; Yamauchi, M.; Yasuhara, T.; Limsirichaikul, S.; Oike, T.; Sato, H.; Held, K.D.; Nakano, T.; Shibata, A. 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation. Oncotarget, 2017, 8(65), 109370-109381.
[http://dx.doi.org/10.18632/oncotarget.22679] [PMID: 29312614]
[42]
Mamouni, K.; Cristini, A.; Guirouilh-Barbat, J.; Monferran, S.; Lemarié, A.; Faye, J.C.; Lopez, B.S.; Favre, G.; Sordet, O. RhoB promotes γH2AX dephosphorylation and DNA double-strand break repair. Mol. Cell. Biol., 2014, 34(16), 3144-3155.
[http://dx.doi.org/10.1128/MCB.01525-13] [PMID: 24912678]
[43]
Said Ahmad, M.; Fazal, F.; Rahman, A.; Hadi, S.M.; Parish, J.H. Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): Correlation with generation of active oxygen species. Carcinogenesis, 1992, 13(4), 605-608.
[http://dx.doi.org/10.1093/carcin/13.4.605] [PMID: 1315626]
[44]
Azmi, A.S.; Bhat, S.H.; Hadi, S.M. Resveratrol-Cu(II) induced DNA breakage in human peripheral lymphocytes: Implications for anticancer properties. FEBS Lett., 2005, 579(14), 3131-3135.
[http://dx.doi.org/10.1016/j.febslet.2005.04.077] [PMID: 15919081]
[45]
Kagawa, T.F.; Geierstanger, B.H.; Wang, A.H.J.; Ho, P.S. Covalent modification of guanine bases in double-stranded DNA. The 1.2-A Z-DNA structure of d(CGCGCG) in the presence of CuCl2. J. Biol. Chem., 1991, 266(30), 20175-20184.
[PMID: 1939078]
[46]
Arif, H.; Sohail, A.; Farhan, M.; Rehman, A.A.; Ahmad, A.; Hadi, S.M. Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: A potential role in cancer chemoprevention. Int. J. Biol. Macromol., 2018, 106, 569-578.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.08.049] [PMID: 28834706]
[47]
Yoshida, D.; Ikeda, Y.; Nakazawa, S. Quantitative analysis of copper, zinc and copper/zinc ratio in selected human brain tumors. J. Neurooncol., 1993, 16(2), 109-115.
[http://dx.doi.org/10.1007/BF01324697] [PMID: 8289088]
[48]
Ebara, M.; Fukuda, H.; Hatano, R.; Saisho, H.; Nagato, Y.; Suzuki, K.; Nakajima, K.; Yukawa, M.; Kondo, F.; Nakayama, A.; Sakurai, H. Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma. J. Hepatol., 2000, 33(3), 415-422.
[http://dx.doi.org/10.1016/S0168-8278(00)80277-9] [PMID: 11019997]
[49]
Zheng, L.F.; Wei, Q.Y.; Cai, Y.J.; Fang, J.G.; Zhou, B.; Yang, L.; Liu, Z.L. DNA damage induced by resveratrol and its synthetic analogues in the presence of Cu (II) ions: Mechanism and structure-activity relationship. Free Radic. Biol. Med., 2006, 41(12), 1807-1816.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.09.007] [PMID: 17157183]
[50]
Arif, H.; Rehmani, N.; Farhan, M.; Ahmad, A.; Hadi, S.M. Mobilization of copper ions by flavonoids in human peripheral lymphocytes leads to oxidative DNA breakage: A structure activity study. Int. J. Mol. Sci., 2015, 16(11), 26754-26769.
[http://dx.doi.org/10.3390/ijms161125992] [PMID: 26569217]
[51]
Safiedeen, Z.; Rodríguez-Gómez, I.; Vergori, L.; Soleti, R.; Vaithilingam, D.; Douma, I.; Agouni, A.; Leiber, D.; Dubois, S.; Simard, G.; Zibara, K.; Andriantsitohaina, R.; Martínez, M.C. Temporal cross talk between endoplasmic reticulum and mitochondria regulates oxidative stress and mediates microparticle-induced endothelial dysfunction. Antioxid. Redox Signal., 2017, 26(1), 15-27.
[http://dx.doi.org/10.1089/ars.2016.6771] [PMID: 27392575]
[52]
Hosseinzadehdehkordi, M.; Adelinik, A.; Tashakor, A. Dual effect of curcumin targets reactive oxygen species, adenosine triphosphate contents and intermediate steps of mitochondria-mediated apoptosis in lung cancer cell lines. Eur. J. Pharmacol., 2015, 769, 203-210.
[http://dx.doi.org/10.1016/j.ejphar.2015.11.019] [PMID: 26593433]
[53]
Oh, B.M.; Lee, S.J.; Cho, H.J.; Park, Y.S.; Kim, J.T.; Yoon, S.R.; Lee, S.C.; Lim, J.S.; Kim, B.Y.; Choe, Y.K.; Lee, H.G. Cystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer. Cell Death Dis., 2017, 8(3)e2682
[http://dx.doi.org/10.1038/cddis.2017.100] [PMID: 28300829]
[54]
Yang, C.; Lim, W.; Bazer, F.W.; Song, G. Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress. Cancer Lett., 2017, 399, 10-19.
[http://dx.doi.org/10.1016/j.canlet.2017.04.014] [PMID: 28428076]
[55]
Bialik, S.; Dasari, S.K.; Kimchi, A. Autophagy-dependent cell death - where, how and why a cell eats itself to death. J. Cell Sci., 2018, 131(18)jcs215152
[http://dx.doi.org/10.1242/jcs.215152] [PMID: 30237248]
[56]
Pott, J.; Kabat, A.M.; Maloy, K.J. Intestinal epithelial cell autophagy is required to protect against tnf-induced apoptosis during chronic colitis in mice. Cell Host Microbe, 2018, 23(2), 191-202.e4.
[http://dx.doi.org/10.1016/j.chom.2017.12.017] [PMID: 29358084]
[57]
Zamudio-Vázquez, R.; Ivanova, S.; Moreno, M.; Hernandez-Alvarez, M.I.; Giralt, E.; Bidon-Chanal, A.; Zorzano, A.; Albericio, F.; Tulla-Puche, J. A new quinoxaline-containing peptide induces apoptosis in cancer cells by autophagy modulation. Chem. Sci. (Camb.), 2015, 6(8), 4537-4549.
[http://dx.doi.org/10.1039/C5SC00125K] [PMID: 29142702]
[58]
Fan, T.; Pi, H.; Li, M.; Ren, Z.; He, Z.; Zhu, F.; Tian, L.; Tu, M.; Xie, J.; Liu, M.; Li, Y.; Tan, M.; Li, G.; Qing, W.; Reiter, R.J.; Yu, Z.; Wu, H.; Zhou, Z. Inhibiting MT2-TFE3-dependent autophagy enhances melatonin-induced apoptosis in tongue squamous cell carcinoma. J. Pineal Res., 2018, 64(2)
[http://dx.doi.org/10.1111/jpi.12457] [PMID: 29149494]
[59]
Cao, J.; Chen, H.; Lu, W.; Wu, Y.; Wu, X.; Xia, D.; Zhu, J. Myricetin induces protective autophagy by inhibiting the phosphorylation of mTOR in HepG2 cells. Anat. Rec. (Hoboken), 2018, 301(5), 786-795.
[http://dx.doi.org/10.1002/ar.23754] [PMID: 29244256]
[60]
Li, J.; Hou, N.; Faried, A.; Tsutsumi, S.; Takeuchi, T.; Kuwano, H. Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells. Ann. Surg. Oncol., 2009, 16(3), 761-771.
[http://dx.doi.org/10.1245/s10434-008-0260-0] [PMID: 19116755]
[61]
Evan, G.I.; Vousden, K.H. Proliferation, cell cycle and apoptosis in cancer. Nature, 2001, 411(6835), 342-348.
[http://dx.doi.org/10.1038/35077213] [PMID: 11357141]
[62]
Roukos, V.; Pegoraro, G.; Voss, T.C.; Misteli, T. Cell cycle staging of individual cells by fluorescence microscopy. Nat. Protoc., 2015, 10(2), 334-348.
[http://dx.doi.org/10.1038/nprot.2015.016] [PMID: 25633629]
[63]
Shapiro, G.I.; Harper, J.W. Anticancer drug targets: Cell cycle and checkpoint control. J. Clin. Invest., 1999, 104(12), 1645-1653.
[http://dx.doi.org/10.1172/JCI9054] [PMID: 10606615]
[64]
Mork, C.N.; Faller, D.V.; Spanjaard, R.A. A mechanistic approach to anticancer therapy: Targeting the cell cycle with histone deacetylase inhibitors. Curr. Pharm. Des., 2005, 11(9), 1091-1104.
[http://dx.doi.org/10.2174/1381612053507567] [PMID: 15853658]
[65]
Johnson, N.; Shapiro, G.I. Cyclin-dependent kinases (cdks) and the DNA damage response: Rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors. Expert Opin. Ther. Targets, 2010, 14(11), 1199-1212.
[http://dx.doi.org/10.1517/14728222.2010.525221] [PMID: 20932174]
[66]
Sánchez-Martínez, C.; Gelbert, L.M.; Lallena, M.J.; de Dios, A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg. Med. Chem. Lett., 2015, 25(17), 3420-3435.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.100] [PMID: 26115571]
[67]
Collins, K.; Jacks, T.; Pavletich, N.P. The cell cycle and cancer. Proc. Natl. Acad. Sci. USA, 1997, 94(7), 2776-2778.
[http://dx.doi.org/10.1073/pnas.94.7.2776] [PMID: 9096291]
[68]
Zhang, X.H.; Zou, Z.Q.; Xu, C.W.; Shen, Y.Z.; Li, D. Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex. Mol. Med. Rep., 2011, 4(2), 273-277.
[PMID: 21468563]
[69]
Schmidt, M.; Rohe, A.; Platzer, C.; Najjar, A.; Erdmann, F.; Sippl, W. Regulation of G2/M transition by inhibition of WEE1 and PKMYT1 kinases. Molecules, 2017, 22(12)E2045
[http://dx.doi.org/10.3390/molecules22122045] [PMID: 29168755]
[70]
Zhang, R.; Shi, H.; Ren, F.; Zhang, M.; Ji, P.; Wang, W.; Liu, C. The aberrant upstream pathway regulations of CDK1 protein were implicated in the proliferation and apoptosis of ovarian cancer cells. J. Ovarian Res., 2017, 10(1), 60.
[http://dx.doi.org/10.1186/s13048-017-0356-x] [PMID: 28899430]
[71]
Qin, J.J.; Li, X.; Hunt, C.; Wang, W.; Wang, H.; Zhang, R. Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine. Genes Dis., 2018, 5(3), 204-219.
[http://dx.doi.org/10.1016/j.gendis.2018.07.002] [PMID: 30320185]
[72]
Kanapathipillai, M. Treating p53 mutant aggregation-associated cancer. Cancers (Basel), 2018, 10(6)E154
[http://dx.doi.org/10.3390/cancers10060154] [PMID: 29789497]
[73]
Gan, W.; Zhao, H.; Li, T.; Liu, K.; Huang, J. CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway. Oncotarget, 2017, 8(42), 71618-71629.
[http://dx.doi.org/10.18632/oncotarget.17794] [PMID: 29069733]
[74]
Lu, M.; Breyssens, H.; Salter, V.; Zhong, S.; Hu, Y.; Baer, C.; Ratnayaka, I.; Sullivan, A.; Brown, N.R.; Endicott, J.; Knapp, S.; Kessler, B.M.; Middleton, M.R.; Siebold, C.; Jones, E.Y.; Sviderskaya, E.V.; Cebon, J.; John, T.; Caballero, O.L.; Goding, C.R.; Lu, X. Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer Cell, 2013, 23(5), 618-633.
[http://dx.doi.org/10.1016/j.ccr.2013.03.013] [PMID: 23623661]
[75]
Shiomi, K.; Kuriyama, I.; Yoshida, H.; Mizushina, Y. Inhibitory effects of myricetin on mammalian DNA polymerase, topoisomerase and human cancer cell proliferation. Food Chem., 2013, 139(1-4), 910-918.
[http://dx.doi.org/10.1016/j.foodchem.2013.01.009] [PMID: 23561189]
[76]
Shay, J.W. Telomeres and aging. Curr. Opin. Cell Biol., 2018, 52, 1-7.
[http://dx.doi.org/10.1016/j.ceb.2017.12.001] [PMID: 29253739]
[77]
Mirjolet, C.; Boidot, R.; Saliques, S.; Ghiringhelli, F.; Maingon, P.; Créhange, G. The role of telomeres in predicting individual radiosensitivity of patients with cancer in the era of personalized radiotherapy. Cancer Treat. Rev., 2015, 41(4), 354-360.
[http://dx.doi.org/10.1016/j.ctrv.2015.02.005] [PMID: 25704912]
[78]
Wu, R.A.; Upton, H.E.; Vogan, J.M.; Collins, K. Telomerase mechanism of telomere synthesis. Annu. Rev. Biochem., 2017, 86, 439-460.
[http://dx.doi.org/10.1146/annurev-biochem-061516-045019] [PMID: 28141967]
[79]
Boldrini, L.; Faviana, P.; Gisfredi, S.; Zucconi, Y.; Di Quirico, D.; Donati, V.; Berti, P.; Spisni, R.; Galleri, D.; Materazzi, G.; Basolo, F.; Miccoli, P.; Pingitore, R.; Fontanini, G. Evaluation of telomerase in the development and progression of colon cancer. Int. J. Mol. Med., 2002, 10(5), 589-592.
[PMID: 12373297]
[80]
Dobija-Kubica, K.; Zalewska-Ziob, M.; Bruliński, K.; Rogoziński, P.; Wiczkowski, A.; Gawrychowska, A.; Gawrychowski, J. Telomerase activity in non-small cell lung cancer. Kardiochir. Torakochirurgia Pol., 2016, 13(1), 15-20.
[http://dx.doi.org/10.5114/kitp.2016.58959] [PMID: 27212973]
[81]
Ceja-Rangel, H.A.; Sánchez-Suárez, P.; Castellanos-Juárez, E.; Peñaroja-Flores, R.; Arenas-Aranda, D.J.; Gariglio, P.; Benítez-Bribiesca, L. Shorter telomeres and high telomerase activity correlate with a highly aggressive phenotype in breast cancer cell lines. Tumour Biol., 2016, 37(9), 11917-11926.
[http://dx.doi.org/10.1007/s13277-016-5045-7] [PMID: 27072825]
[82]
Mondal, S.; Jana, J.; Sengupta, P.; Jana, S.; Chatterjee, S. Myricetin arrests human telomeric G-quadruplex structure: A new mechanistic approach as an anticancer agent. Mol. Biosyst., 2016, 12(8), 2506-2518.
[http://dx.doi.org/10.1039/C6MB00218H] [PMID: 27249025]
[83]
Phan, A.T.; Kuryavyi, V.; Patel, D.J. DNA architecture: From G to Z. Curr. Opin. Struct. Biol., 2006, 16(3), 288-298.
[http://dx.doi.org/10.1016/j.sbi.2006.05.011] [PMID: 16714104]
[84]
Xu, Y.; Ishizuka, T.; Kurabayashi, K.; Komiyama, M. Consecutive formation of G-quadruplexes in human telomeric-overhang DNA: A protective capping structure for telomere ends. Angew. Chem. Int. Ed. Engl., 2009, 48(42), 7833-7836.
[http://dx.doi.org/10.1002/anie.200903858] [PMID: 19757477]
[85]
Balasubramanian, S.; Hurley, L.H.; Neidle, S. Targeting G-quadruplexes in gene promoters: A novel anticancer strategy? Nat. Rev. Drug Discov., 2011, 10(4), 261-275.
[http://dx.doi.org/10.1038/nrd3428] [PMID: 21455236]
[86]
Bai, Z.G.; Zhang, Z.T. A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer. OncoTargets Ther., 2018, 11, 7077-7087.
[http://dx.doi.org/10.2147/OTT.S169484] [PMID: 30410364]
[87]
Dhani, N.C.; Oza, A.M. Targeting angiogenesis: Taming the medusa of ovarian cancer. Hematol. Oncol. Clin. North Am., 2018, 32(6), 1041-1055.
[http://dx.doi.org/10.1016/j.hoc.2018.07.008] [PMID: 30390759]
[88]
Jabłońska-Trypuć, A.; Matejczyk, M.; Rosochacki, S. Matrix metalloproteinases (MMPs), the main Extracellular Matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J. Enzyme Inhib. Med. Chem., 2016, 31(Suppl. 1), 177-183.
[89]
Huang, H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors (Basel), 2018, 18(10)E3249
[http://dx.doi.org/10.3390/s18103249] [PMID: 30262739]
[90]
Yang, J.; Min, K-W.; Kim, D-H.; Son, B.K.; Moon, K.M.; Wi, Y.C.; Bang, S.S.; Oh, Y.H.; Do, S.I.; Chae, S.W.; Oh, S.; Kim, Y.H.; Kwon, M.J. High TNFRSF12A level associated with MMP-9 overexpression is linked to poor prognosis in breast cancer: Gene set enrichment analysis and validation in large-scale cohorts. PLoS One, 2018, 13(8)e0202113
[http://dx.doi.org/10.1371/journal.pone.0202113] [PMID: 30142200]
[91]
Yao, Z.; Yuan, T.; Wang, H.; Yao, S.; Zhao, Y.; Liu, Y.; Jin, S.; Chu, J.; Xu, Y.; Zhou, W.; Yang, S.; Liu, Y. MMP-2 together with MMP-9 overexpression correlated with lymph node metastasis and poor prognosis in early gastric carcinoma. Tumour Biol., 2017, 39(6)
[http://dx.doi.org/10.1177/1010428317700411] [PMID: 28621235]
[92]
Shih, Y.W.; Wu, P.F.; Lee, Y.C.; Shi, M.D.; Chiang, T.A. Myricetin suppresses invasion and migration of human lung adenocarcinoma A549 cells: possible mediation by blocking the ERK signaling pathway. J. Agric. Food Chem., 2009, 57(9), 3490-3499.
[http://dx.doi.org/10.1021/jf900124r] [PMID: 19326946]
[93]
Asuthkar, S.; Stepanova, V.; Lebedeva, T.; Holterman, A.L.; Estes, N.; Cines, D.B.; Rao, J.S.; Gondi, C.S. Multifunctional roles of urokinase Plasminogen Activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer. Mol. Biol. Cell, 2013, 24(17), 2620-2632.
[http://dx.doi.org/10.1091/mbc.e12-04-0306] [PMID: 23864708]
[94]
Meng, D.; Lei, M.; Han, Y.; Zhao, D.; Zhang, X.; Yang, Y.; Liu, R. MicroRNA-645 targets urokinase Plasminogen Activator and decreases the invasive growth of MDA-MB-231 triple-negative breast cancer cells. OncoTargets Ther., 2018, 11, 7733-7743.
[http://dx.doi.org/10.2147/OTT.S187221] [PMID: 30464522]
[95]
Bertl, E.; Bartsch, H.; Gerhäuser, C. Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol. Cancer Ther., 2006, 5(3), 575-585.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0324] [PMID: 16546971]
[96]
Larsen, A.K.; Ouaret, D.; El Ouadrani, K.; Petitprez, A. Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacol. Ther., 2011, 131(1), 80-90.
[http://dx.doi.org/10.1016/j.pharmthera.2011.03.012] [PMID: 21439312]
[97]
Chen, J.; Yuan, W.; Wu, L.; Tang, Q.; Xia, Q.; Ji, J.; Liu, Z.; Ma, Z.; Zhou, Z.; Cheng, Y.; Shu, X. PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway. Oncotarget, 2017, 8(6), 9961-9973.
[http://dx.doi.org/10.18632/oncotarget.14283] [PMID: 28035069]
[98]
Feng, Q.; Zhang, C.; Lum, D.; Druso, J.E.; Blank, B.; Wilson, K.F.; Welm, A.; Antonyak, M.A.; Cerione, R.A. A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis. Nat. Commun., 2017, 8, 14450.
[http://dx.doi.org/10.1038/ncomms14450] [PMID: 28205552]
[99]
Mo, M.; Yang, J.; Zhu, X.; Zhu, J. Bevacizumab maintenance in metastatic colorectal cancer. J. Clin. Oncol., 2018, 36(23), 2451-2452.
[http://dx.doi.org/10.1200/JCO.2018.78.3795] [PMID: 29863975]
[100]
Miller, K.D.; O’Neill, A.; Gradishar, W.; Hobday, T.J.; Goldstein, L.J.; Mayer, I.A.; Bloom, S.; Brufsky, A.M.; Tevaarwerk, A.J.; Sparano, J.A.; Le-Lindqwister, N.A.B.; Hendricks, C.; Northfelt, D.W.; Dang, C.T. Jr G.W.S. Double-blind phase iii trial of adjuvant chemotherapy with and without bevacizumab in patientswith lymph node–positive and high-risk lymph node–negative breast cancer (e5103). J. Clin. Oncol., 2018, 36(25), 2621-2629.
[http://dx.doi.org/10.1200/JCO.2018.79.2028] [PMID: 30040523]
[101]
Kim, J.D.; Liu, L.; Guo, W.; Meydani, M. Chemical structure of flavonols in relation to modulation of angiogenesis and immune-endothelial cell adhesion. J. Nutr. Biochem., 2006, 17(3), 165-176.
[http://dx.doi.org/10.1016/j.jnutbio.2005.06.006] [PMID: 16169200]
[102]
Huang, H.; Chen, A.Y.; Rojanasakul, Y.; Ye, X.; Rankin, G.O.; Chen, Y.C. Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J. Funct. Foods, 2015, 15, 464-475.
[http://dx.doi.org/10.1016/j.jff.2015.03.051] [PMID: 26113875]
[103]
Hasegawa, Y.; Murph, M.; Yu, S.; Tigyi, G.; Mills, G.B. Lysophosphatidic acid (LPA)-induced vasodilator-stimulated phosphoprotein mediates lamellipodia formation to initiate motility in PC-3 prostate cancer cells. Mol. Oncol., 2008, 2(1), 54-69.
[http://dx.doi.org/10.1016/j.molonc.2008.03.009] [PMID: 19081821]
[104]
Kim, K.B.; Yi, J.S.; Nguyen, N.; Lee, J.H.; Kwon, Y.C.; Ahn, B.Y.; Cho, H.; Kim, Y.K.; Yoo, H.J.; Lee, J.S.; Ko, Y.G. Cell-surface receptor for complement component C1q (gC1qR) is a key regulator for lamellipodia formation and cancer metastasis. J. Biol. Chem., 2011, 286(26), 23093-23101.
[http://dx.doi.org/10.1074/jbc.M111.233304] [PMID: 21536672]
[105]
Small, J.V.; Stradal, T.; Vignal, E.; Rottner, K. The lamellipodium: where motility begins. Trends Cell Biol., 2002, 12(3), 112-120.
[http://dx.doi.org/10.1016/S0962-8924(01)02237-1] [PMID: 11859023]
[106]
Yin, M.; Ma, W.; An, L. Cortactin in cancer cell migration and invasion. Oncotarget, 2017, 8(50), 88232-88243.
[http://dx.doi.org/10.18632/oncotarget.21088] [PMID: 29152154]
[107]
Lai, F.P.L.; Szczodrak, M.; Oelkers, J.M.; Ladwein, M.; Acconcia, F.; Benesch, S.; Auinger, S.; Faix, J.; Small, J.V.; Polo, S.; Stradal, T.E.B.; Rottner, K. Cortactin promotes migration and platelet-derived growth factor-induced actin reorganization by signaling to Rho-GTPases. Mol. Biol. Cell, 2009, 20(14), 3209-3223.
[http://dx.doi.org/10.1091/mbc.e08-12-1180] [PMID: 19458196]
[108]
Innocenti, M.; Zucconi, A.; Disanza, A.; Frittoli, E.; Areces, L.B.; Steffen, A.; Stradal, T.E.B.; Di Fiore, P.P.; Carlier, M.F.; Scita, G. Abi1 is essential for the formation and activation of a WAVE2 signalling complex. Nat. Cell Biol., 2004, 6(4), 319-327.
[http://dx.doi.org/10.1038/ncb1105] [PMID: 15048123]
[109]
Arthur, W.T.; Quilliam, L.A.; Cooper, J.A. Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. J. Cell Biol., 2004, 167(1), 111-122.
[http://dx.doi.org/10.1083/jcb.200404068] [PMID: 15479739]
[110]
Di, J.; Cao, H.; Tang, J.; Lu, Z.; Gao, K.; Zhu, Z.; Zheng, J. Rap2B promotes cell proliferation, migration and invasion in prostate cancer. Med. Oncol., 2016, 33(6), 58.
[http://dx.doi.org/10.1007/s12032-016-0771-7] [PMID: 27154636]
[111]
Newell-Litwa, K.A.; Badoual, M.; Asmussen, H.; Patel, H.; Whitmore, L.; Horwitz, A.R. ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity. J. Cell Biol., 2015, 210(2), 225-242.
[http://dx.doi.org/10.1083/jcb.201504046] [PMID: 26169356]
[112]
Strobel, P.; Allard, C.; Perez-Acle, T.; Calderon, R.; Aldunate, R.; Leighton, F. Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochem. J., 2005, 386(Pt 3), 471-478.
[http://dx.doi.org/10.1042/BJ20040703] [PMID: 15469417]
[113]
Cretella, D.; Ravelli, A.; Fumarola, C.; La Monica, S.; Digiacomo, G.; Cavazzoni, A.; Alfieri, R.; Biondi, A.; Generali, D.; Bonelli, M.; Petronini, P.G. The anti-tumor efficacy of CDK4/6 inhibition is enhanced by the combination with PI3K/AKT/mTOR inhibitors through impairment of glucose metabolism in TNBC cells. J. Exp. Clin. Cancer Res., 2018, 37(1), 72.
[http://dx.doi.org/10.1186/s13046-018-0741-3] [PMID: 29587820]
[114]
Holder, S.L.; Abdulkadir, S.A. PIM1 kinase as a target in prostate cancer: roles in tumorigenesis, castration resistance, and docetaxel resistance. Curr. Cancer Drug Targets, 2014, 14(2), 105-114.
[http://dx.doi.org/10.2174/1568009613666131126113854] [PMID: 24274399]
[115]
Zhao, W.; Qiu, R.; Li, P.; Yang, J. PIM1: A promising target in patients with triple-negative breast cancer. Med. Oncol., 2017, 34(8), 142.
[http://dx.doi.org/10.1007/s12032-017-0998-y] [PMID: 28721678]
[116]
Scala, S. Molecular pathways: Targeting the CXCR4–CXCL12 axis—untapped potential in the tumor microenvironment. Clin. Cancer Res., 2015, 21(19), 4278-4285.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0914] [PMID: 26199389]
[117]
Sleightholm, R.L.; Neilsen, B.K.; Li, J.; Steele, M.M.; Singh, R.K.; Hollingsworth, M.A.; Oupicky, D. Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy. Pharmacol. Ther., 2017, 179, 158-170.
[http://dx.doi.org/10.1016/j.pharmthera.2017.05.012] [PMID: 28549596]
[118]
Santio, N.M.; Eerola, S.K.; Paatero, I.; Yli-Kauhaluoma, J.; Anizon, F.; Moreau, P.; Tuomela, J.; Härkönen, P.; Koskinen, P.J. Pim kinases promote migration and metastatic growth of prostate cancer xenografts. PLoS One, 2015, 10(6)e0130340
[http://dx.doi.org/10.1371/journal.pone.0130340] [PMID: 26075720]
[119]
Grivennikov, S.I. Inflammation and colorectal cancer: Colitis-associated neoplasia. Semin. Immunopathol., 2013, 35(2), 229-244.
[http://dx.doi.org/10.1007/s00281-012-0352-6] [PMID: 23161445]
[120]
Sebio, A.; Kahn, M.; Lenz, H-J. The potential of targeting Wnt/β-catenin in colon cancer. Expert Opin. Ther. Targets, 2014, 18(6), 611-615.
[http://dx.doi.org/10.1517/14728222.2014.906580] [PMID: 24702624]
[121]
Cheng, X.; Xu, X.; Chen, D.; Zhao, F.; Wang, W. Therapeutic potential of targeting the Wnt/β-catenin signaling pathway in colorectal cancer. Biomed. Pharmacother., 2019, 110, 473-481.
[http://dx.doi.org/10.1016/j.biopha.2018.11.082] [PMID: 30530050]
[122]
Wang, B.; Tian, T.; Kalland, K.H.; Ke, X.; Qu, Y. Targeting Wnt/β-catenin signaling for cancer immunotherapy. Trends Pharmacol. Sci., 2018, 39(7), 648-658.
[http://dx.doi.org/10.1016/j.tips.2018.03.008] [PMID: 29678298]
[123]
Amado, N.G.; Predes, D.; Moreno, M.M.; Carvalho, I.O.; Mendes, F.A.; Abreu, J.G. Flavonoids and Wnt/β-catenin signaling: Potential role in colorectal cancer therapies. Int. J. Mol. Sci., 2014, 15(7), 12094-12106.
[http://dx.doi.org/10.3390/ijms150712094] [PMID: 25007066]
[124]
Li, L.; Fu, X.; Zhang, W.; Xiao, L.; Qiu, Y.; Peng, Y.; Shi, L.; Chen, X.; Zhou, X.; Deng, M. Wnt signaling pathway is activated in right colon serrated polyps correlating to specific molecular form of β-catenin. Hum. Pathol., 2013, 44(6), 1079-1088.
[http://dx.doi.org/10.1016/j.humpath.2012.09.013] [PMID: 23317545]
[125]
Staal, F.J.T.; Sen, J.M. The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur. J. Immunol., 2008, 38(7), 1788-1794.
[http://dx.doi.org/10.1002/eji.200738118] [PMID: 18581335]
[126]
Luqman, S.; Pezzuto, J.M. NFkappaB: A promising target for natural products in cancer chemoprevention. Phytother. Res., 2010, 24(7), 949-963.
[PMID: 20577970]
[127]
Zhang, M.J.; Su, H.; Yan, J.Y.; Li, N.; Song, Z.Y.; Wang, H.J.; Huo, L.G.; Wang, F.; Ji, W.S.; Qu, X.J.; Qu, M.H. Chemopreventive effect of Myricetin, a natural occurring compound, on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. Biomed. Pharmacother., 2018, 97, 1131-1137.
[http://dx.doi.org/10.1016/j.biopha.2017.11.018] [PMID: 29136951]
[128]
Asati, V.; Mahapatra, D.K.; Bharti, S.K. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur. J. Med. Chem., 2016, 109, 314-341.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.012] [PMID: 26807863]
[129]
Roberts, P.J.; Der, C.J. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene, 2007, 26(22), 3291-3310.
[http://dx.doi.org/10.1038/sj.onc.1210422] [PMID: 17496923]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy