Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Mini-Review Article

Phytochemicals in the Synthetic Era: A Potential Oncosuppressor against Cancer Stem Cells

Author(s): Devangkumar Maru and Anmol Kumar*

Volume 23, Issue 11, 2023

Published on: 22 March, 2023

Page: [1242 - 1252] Pages: 11

DOI: 10.2174/1871520623666230227113239

Price: $65


CSCs (Cancer stem cells) are a subpopulation of transformed cells residing within the tumour that possesses properties of stem cells, like self-renewal and differentiation. Different signalling pathways, epigenetic changes, and interaction with a tumour microenvironment are found to be involved in the maintenance of stemness of CSCs and contribute to chemoresistance. Hence, it is difficult to prevent and control progression completely without considering CSCs as a crucial target. Some phytochemicals target different pathways and gene expression and modulate CSC markers to suppress the stemness properties of cancer cells. Thus, phytochemicals potentially impact CSCs which may be applied in chemo-prevention. This comprehensive review discusses some studied phytochemicals that suppress stemness characters in various cancer types both in vitro and in vivo animal models. However, the chemo-prevention ability of phytochemicals needs to be validated in further subsequent stages of clinical trials.

Keywords: Cancer stem cell, phytochemicals, chemoresistance, chemoprevention, biomarker, epigenetic changes.

Graphical Abstract
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[] [PMID: 33538338]
Nagai, H.; Kim, Y.H. Cancer prevention from the perspective of global cancer burden patterns. J. Thorac. Dis., 2017, 9(3), 448-451.
[] [PMID: 28449441]
Yu, Z.; Pestell, T.G.; Lisanti, M.P.; Pestell, R.G. Cancer stem cells. Int. J. Biochem. Cell Biol., 2012, 44(12), 2144-2151.
[] [PMID: 22981632]
Rossi, F.; Noren, H.; Jove, R.; Beljanski, V.; Grinnemo, K.H. Differences and similarities between cancer and somatic stem cells: Thera-peutic implications. Stem Cell Res. Ther., 2020, 11(1), 489.
[] [PMID: 33208173]
Prieto-Vila, M.; Takahashi, R.; Usuba, W.; Kohama, I.; Ochiya, T. Drug resistance driven by cancer stem cells and their niche. Int. J. Mol. Sci., 2017, 18(12), 2574.
[] [PMID: 29194401]
Chu, D.T.; Nguyen, T.T.; Tien, N.L.B.; Tran, D.K.; Jeong, J.H.; Anh, P.G.; Thanh, V.V.; Truong, D.T.; Dinh, T.C. Recent progress of stem cell therapy in cancer treatment: Molecular mechanisms and potential applications. Cells, 2020, 9(3), 563.
[] [PMID: 32121074]
Liskova, A.; Kubatka, P.; Samec, M.; Zubor, P.; Mlyncek, M.; Bielik, T.; Samuel, S.M.; Zulli, A.; Kwon, T.K.; Büsselberg, D. Dietary phytochemicals targeting cancer stem cells. Molecules, 2019, 24(5), 899.
[] [PMID: 30836718]
Peitzsch, C.; Tyutyunnykova, A.; Pantel, K.; Dubrovska, A. Cancer stem cells: The root of tumor recurrence and metastases. Semin. Cancer Biol., 2017, 44, 10-24.
[] [PMID: 28257956]
Yang, L.; Shi, P.; Zhao, G.; Xu, J.; Peng, W.; Zhang, J.; Zhang, G.; Wang, X.; Dong, Z.; Chen, F.; Cui, H. Targeting cancer stem cell path-ways for cancer therapy. Signal Transduct. Target. Ther., 2020, 5(1), 1-35.
Afify, S.M.; Sanchez Calle, A.; Hassan, G.; Kumon, K.; Nawara, H.M.; Zahra, M.H.; Mansour, H.M.; Khayrani, A.C.; Alam, M.J.; Du, J.; Seno, A.; Iwasaki, Y.; Seno, M. A novel model of liver cancer stem cells developed from induced pluripotent stem cells. Br. J. Cancer, 2020, 122(9), 1378-1390.
[] [PMID: 32203212]
Skvortsov, S.; Debbage, P.; Lukas, P.; Skvortsova, I. Crosstalk between DNA repair and cancer stem cell (CSC) associated intracellular pathways. Semin. Cancer Biol., 2015, 31, 36-42.
[] [PMID: 24954010]
Doherty, M.; Smigiel, J.; Junk, D.; Jackson, M. Cancer stem cell plasticity drives therapeutic resistance. Cancers, 2016, 8(1), 8.
[] [PMID: 26742077]
Walcher, L.; Kistenmacher, A.K.; Suo, H.; Kitte, R.; Dluczek, S.; Strauß, A.; Blaudszun, A.R.; Yevsa, T.; Fricke, S.; Kossatz-Boehlert, U. Cancer stem cells-origins and biomarkers: Perspectives for targeted personalized therapies. Front. Immunol., 2020, 11, 1280.
Thapa, R.; Wilson, G.D. The importance of CD44 as a stem cell biomarker and therapeutic target in cancer. Stem Cells Int., 2016, 2016, 2087204.
[] [PMID: 27200096]
Mohiuddin, I.S.; Wei, S.J.; Kang, M.H. Role of OCT4 in cancer stem-like cells and chemotherapy resistance. Biochim. Biophys. Acta Mol. Basis Dis., 2020, 1866(4), 165432.
[] [PMID: 30904611]
Zhang, S.; Xiong, X.; Sun, Y. Functional characterization of SOX2 as an anticancer target. Signal Transduct. Target. Ther., 2020, 5(1), 135.
[] [PMID: 32728033]
Warrier, N.M.; Agarwal, P.; Kumar, P. Emerging importance of survivin in stem cells and cancer: The development of new cancer thera-peutics. Stem Cell Rev. Rep., 2020, 16(5), 828-852.
[] [PMID: 32691369]
Brugnoli, F.; Grassilli, S.; Al-Qassab, Y.; Capitani, S.; Bertagnolo, V. CD133 in breast cancer cells: More than a stem cell marker. J. Oncol., 2019, 2019, 7512632.
[] [PMID: 31636668]
Matsika, A.; Srinivasan, B.; Day, C.; Mader, S.A.; Margaret Kiernan, D.; Broomfield, A.; Fu, J.; Hooper, J.D.; Kench, J.G.; Samaratunga, H. Cancer stem cell markers in prostate cancer: An immunohistochemical study of ALDH1, SOX2 and EZH2. Pathology, 2015, 47(7), 622-628.
[] [PMID: 26517640]
Tsunekuni, K.; Konno, M.; Haraguchi, N.; Koseki, J.; Asai, A.; Matsuoka, K.; Kobunai, T.; Takechi, T.; Doki, Y.; Mori, M.; Ishii, H. CD44/CD133-positive colorectal cancer stem cells are sensitive to trifluridine exposure. Sci. Rep., 2019, 9(1), 14861.
[] [PMID: 31619711]
Maiuthed, A.; Chantarawong, W.; Chanvorachote, P. Lung cancer stem cells and cancer stem cell-targeting natural compounds. Anticancer Res., 2018, 38(7), 3797-3809.
[] [PMID: 29970499]
Xiao, Y.; Lin, M.; Jiang, X.; Ye, J.; Guo, T.; Shi, Y.; Bian, X. The recent advances on liver cancer stem cells: Biomarkers, separation, and therapy. Anal. Cell. Pathol., 2017, 2017, 5108653.
[] [PMID: 28819584]
Wang, X.; Huang, S.; Chen, J.L. Understanding of leukemic stem cells and their clinical implications. Mol. Cancer, 2017, 16(1), 2.
[] [PMID: 28137304]
Xu, H-S.; Qin, X.L.; Zong, H.L.; He, X.G.; Cao, L. Cancer stem cell markers in glioblastoma - an update. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(14), 3207-3211.
[PMID: 28770964]
Ishiwata, T.; Matsuda, Y.; Yoshimura, H.; Sasaki, N.; Ishiwata, S.; Ishikawa, N.; Takubo, K.; Arai, T.; Aida, J. Pancreatic cancer stem cells: Features and detection methods. Pathol. Oncol. Res., 2018, 24(4), 797-805.
[] [PMID: 29948612]
Keyvani, V.; Farshchian, M.; Esmaeili, S.A.; Yari, H.; Moghbeli, M.; Nezhad, S.R.K.; Abbaszadegan, M.R. Ovarian cancer stem cells and targeted therapy. J. Ovarian Res., 2019, 12(1), 120.
[] [PMID: 31810474]
Cochrane, C.; Szczepny, A.; Watkins, D.; Cain, J. Hedgehog signaling in the maintenance of cancer stem cells. Cancers, 2015, 7(3), 1554-1585.
[] [PMID: 26270676]
Justilien, V.; Walsh, M.P.; Ali, S.A.; Thompson, E.A.; Murray, N.R.; Fields, A.P. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma. Cancer Cell, 2014, 25(2), 139-151.
[] [PMID: 24525231]
Abe, Y.; Tanaka, N. The hedgehog signaling networks in lung cancer: The mechanisms and roles in tumor progression and implications for cancer therapy. BioMed Res. Int., 2016, 2016, 7969286.
[] [PMID: 28105432]
Mohammed, M.K.; Shao, C.; Wang, J.; Wei, Q.; Wang, X.; Collier, Z.; Tang, S.; Liu, H.; Zhang, F.; Huang, J.; Guo, D.; Lu, M.; Liu, F.; Liu, J.; Ma, C.; Shi, L.L.; Athiviraham, A.; He, T.C.; Lee, M.J. Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance. Genes Dis., 2016, 3(1), 11-40.
[] [PMID: 27077077]
Holland, J.D.; Klaus, A.; Garratt, A.N.; Birchmeier, W. Wnt signaling in stem and cancer stem cells. Curr. Opin. Cell Biol., 2013, 25(2), 254-264.
[] [PMID: 23347562]
Zhang, Y.; Wang, X. Targeting the Wnt/β-catenin signaling pathway in cancer. J. Hematol. Oncol., 2020, 13(1), 165.
[] [PMID: 33276800]
Xia, P.; Xu, X-Y.Y. PI3K/Akt/mTOR signaling pathway in cancer stem cells: From basic research to clinical application. Am. J. Cancer Res., 2015, 5(5), 1602-1609.
[PMID: 26175931]
Yoon, C.; Lu, J.; Yi, B.C.; Chang, K.K.; Simon, M.C.; Ryeom, S.; Yoon, S.S. PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas. Oncogenesis, 2021, 10(1), 12.
[] [PMID: 33468992]
Wei, Y.; Jiang, Y.; Zou, F.; Liu, Y.; Wang, S.; Xu, N.; Xu, W.; Cui, C.; Xing, Y.; Liu, Y.; Cao, B.; Liu, C.; Wu, G.; Ao, H.; Zhang, X.; Jiang, J. Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells. Proc. Natl. Acad. Sci. USA, 2013, 110(17), 6829-6834.
[] [PMID: 23569237]
Venkatesh, V.; Nataraj, R.; Thangaraj, G.S.; Karthikeyan, M.; Gnanasekaran, A.; Kaginelli, S.B.; Kuppanna, G.; Kallappa, C.G.; Basalin-gappa, K.M. Targeting Notch signalling pathway of cancer stem cells. Stem Cell Investig., 2018, 5(2), 5.
[] [PMID: 29682512]
Meisel, C.T.; Porcheri, C.; Mitsiadis, T.A. Cancer stem cells, Quo Vadis? the notch signaling pathway in tumor initiation and progression. Cells, 2020, 9(8), 1879.
[] [PMID: 32796631]
Xiao, W.; Gao, Z.; Duan, Y.; Yuan, W.; Ke, Y. Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma. J. Exp. Clin. Cancer Res., 2017, 36(1), 41.
[] [PMID: 28279221]
Dandawate, P.R.; Subramaniam, D.; Jensen, R.A.; Anant, S. Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy. Semin. Cancer Biol., 2016, 40-41(41), 192-208.
[] [PMID: 27609747]
Park, S.Y.; Lee, C.J.; Choi, J.H.; Kim, J.H.; Kim, J.W.; Kim, J.Y.; Nam, J.S. The JAK2/STAT3/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance. J. Exp. Clin. Cancer Res., 2019, 38(1), 399.
[] [PMID: 31511084]
Dolatabadi, S.; Jonasson, E.; Lindén, M.; Fereydouni, B.; Bäcksten, K.; Nilsson, M.; Martner, A.; Forootan, A.; Fagman, H.; Landberg, G.; Åman, P.; Ståhlberg, A. JAK-STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposar-coma. Int. J. Cancer, 2019, 145(2), 435-449.
[] [PMID: 30650179]
Ribatti, D.; Tamma, R.; Annese, T. Epithelial-mesenchymal transition in cancer: A historical overview. Transl. Oncol., 2020, 13(6), 100773.
[] [PMID: 32334405]
Gonzalez, D.M.; Medici, D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci. Signal., 2014, 7(344), re8.
[] [PMID: 25249658]
Babaei, G.; Aziz, S.G.G.; Jaghi, N.Z.Z. EMT, cancer stem cells and autophagy; The three main axes of metastasis. Biomed. Pharmacother., 2021, 133, 110909.
[] [PMID: 33227701]
Chen, S.; Fisher, R.C.; Signs, S.; Molina, L.A.; Shenoy, A.K.; Lopez, M.C.; Baker, H.V.; Koomen, J.M.; Chen, Y.; Gittleman, H. Barn-holtz-Sloan, J.; Berg, A.; Appelman, H.D.; Huang, E.H. Inhibition of PI3K/Akt/mTOR signaling in PI3KR2-overexpressing colon cancer stem cells reduces tumor growth due to apoptosis. Oncotarget, 2017, 8(31), 50476-50488.
[] [PMID: 28881576]
He, Y.C.; Zhou, F.L.; Shen, Y.; Liao, D.F.; Cao, D. Apoptotic death of cancer stem cells for cancer therapy. Int. J. Mol. Sci., 2014, 15(5), 8335-8351.
[] [PMID: 24823879]
Sabnis, N.G.; Miller, A.; Titus, M.A.; Huss, W.J. The efflux transporter ABCG2 maintains prostate stem cells. Mol. Cancer Res., 2017, 15(2), 128-140.
[] [PMID: 27856956]
Ko, J.H.; Sethi, G.; Um, J.Y.; Shanmugam, M.K.; Arfuso, F.; Kumar, A.P.; Bishayee, A.; Ahn, K.S. The role of resveratrol in cancer thera-py. Int. J. Mol. Sci., 2017, 18(12), 2589.
[] [PMID: 29194365]
Peng, L.; Jiang, D. Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition. PLoS One, 2018, 13(10), e0205918.
[] [PMID: 30356255]
Shen, Y.A.; Lin, C.H.; Chi, W.H.; Wang, C.Y.; Hsieh, Y.T.; Wei, Y.H.; Chen, Y.J. Resveratrol impedes the stemness, epithelial-mesenchymal transition, and metabolic reprogramming of cancer stem cells in nasopharyngeal carcinoma through p53 activation. Evid. Based Complement. Alternat. Med., 2013, 2013, 590393.
[] [PMID: 590393]
Pouyafar, A.; Zadi Heydarabad, M.; Aghdam, S.B.; Khaksar, M.; Azimi, A.; Rahbarghazi, R.; Talebi, M. Resveratrol potentially increased the tumoricidal effect of doxorubicin on SKOV3 cancer stem cells in vitro. J. Cell. Biochem., 2019, 120(5), 8430-8437.
[] [PMID: 30609135]
Sun, H.; Zhang, T.; Liu, R.; Cao, W.; Zhang, Z.; Liu, Z.; Qian, W.; Wang, D.; Yu, D.; Zhong, C. Resveratrol inhibition of renal cancer stem cell characteristics and modulation of the sonic hedgehog pathway. Nutr. Cancer, 2021, 73(7), 1157-1167.
[] [PMID: 32586140]
Fu, Y.; Chang, H.; Peng, X.; Bai, Q.; Yi, L.; Zhou, Y.; Zhu, J.; Mi, M. Resveratrol inhibits breast cancer stem-like cells and induces au-tophagy via suppressing Wnt/β-catenin signaling pathway. PLoS One, 2014, 9(7), e102535.
[] [PMID: 25068516]
Namiki, K.; Wongsirisin, P.; Yokoyama, S.; Sato, M.; Rawangkan, A.; Sakai, R.; Iida, K.; Suganuma, M. (-)-Epigallocatechin gallate inhib-its stemness and tumourigenicity stimulated by AXL receptor tyrosine kinase in human lung cancer cells. Sci. Rep., 2020, 10(1), 2444.
[] [PMID: 32051483]
Lee, S.H.; Nam, H.J.; Kang, H.J.; Kwon, H.W.; Lim, Y.C. Epigallocatechin-3-gallate attenuates head and neck cancer stem cell traits through suppression of Notch pathway. Eur. J. Cancer, 2013, 49(15), 3210-3218.
[] [PMID: 23876835]
Sun, X.; Song, J.; Li, E.; Geng, H.; Li, Y.; Yu, D.; Zhong, C. () Epigallocatechin 3 gallate inhibits bladder cancer stem cells via suppres-sion of sonic hedgehog pathway. Oncol. Rep., 2019, 42(1), 425-435.
[] [PMID: 31180522]
Jiang, P.; Xu, C.; Zhang, P.; Ren, J.; Mageed, F.; Wu, X.; Chen, L.; Zeb, F.; Feng, Q.; Li, S. Epigallocatechin 3 gallate inhibits self renewal ability of lung cancer stem like cells through inhibition of CLOCK. Int. J. Mol. Med., 2020, 46(6), 2216-2224.
[] [PMID: 33125096]
Fujiki, H.; Sueoka, E.; Rawangkan, A.; Suganuma, M. Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate. J. Cancer Res. Clin. Oncol., 2017, 143(12), 2401-2412.
[] [PMID: 28942499]
Mineva, N.D.; Paulson, K.E.; Naber, S.P.; Yee, A.S.; Sonenshein, G.E. Epigallocatechin-3-gallate inhibits stem-like inflammatory breast cancer cells. PLoS One, 2013, 8(9), e73464.
[] [PMID: 24039951]
Zhang, L.; Li, L.; Jiao, M.; Wu, D.; Wu, K.; Li, X.; Zhu, G.; Yang, L.; Wang, X.; Hsieh, J.T.; He, D. Genistein inhibits the stemness proper-ties of prostate cancer cells through targeting Hedgehog-Gli1 pathway. Cancer Lett., 2012, 323(1), 48-57.
[] [PMID: 22484470]
Zhang, Q.; Cao, W.S.; Wang, X.Q.; Zhang, M.; Lu, X.M.; Chen, J.Q.; Chen, Y.; Ge, M.M.; Zhong, C.Y.; Han, H.Y. Genistein inhibits naso-pharyngeal cancer stem cells through sonic hedgehog signaling. Phytother. Res., 2019, 33(10), 2783-2791.
[] [PMID: 31342620]
Wang, M.; Jiang, S.; Zhou, L.; Yu, F.; Ding, H.; Li, P.; Zhou, M.; Wang, K. Potential mechanisms of action of curcumin for cancer preven-tion: focus on cellular signaling pathways and miRNAs. Int. J. Biol. Sci., 2019, 15(6), 1200-1214.
[] [PMID: 31223280]
Sordillo, P.P.; Helson, L. Curcumin and cancer stem cells: Curcumin has asymmetrical effects on cancer and normal stem cells. Anticancer Res., 2015, 35(2), 599-614.
[PMID: 25667437]
Huang, Y.T.; Lin, Y.W.; Chiu, H.M.; Chiang, B.H. Curcumin induces apoptosis of colorectal cancer stem cells by coupling with CD44 marker. J. Agric. Food Chem., 2016, 64(11), 2247-2253.
[] [PMID: 26906122]
Wang, J.; Wang, C.; Bu, G. Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein ki-nase B/mammalian target of rapamycin signaling pathway. Exp. Ther. Med., 2018, 15(4), 3650-3658.
[] [PMID: 29545895]
Zhou, Q.; Ye, M.; Lu, Y.; Zhang, H.; Chen, Q.; Huang, S.; Su, S. Curcumin improves the tumoricidal effect of mitomycin C by suppress-ing ABCG2 expression in stem cell-like breast cancer cells. PLoS One, 2015, 10(8), e0136694.
[] [PMID: 26305906]
Simões, B.M.; Santiago-Gómez, A.; Chiodo, C.; Moreira, T.; Conole, D.; Lovell, S.; Alferez, D.; Eyre, R.; Spence, K.; Sarmiento-Castro, A.; Kohler, B.; Morisset, L.; Lanzino, M.; Andò, S.; Marangoni, E.; Sims, A.H.; Tate, E.W.; Howell, S.J.; Clarke, R.B. Targeting STAT3 signaling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer. Oncogene, 2020, 39(25), 4896-4908.
[] [PMID: 32472077]
Ge, M.; Zhang, L.; Cao, L.; Xie, C.; Li, X.; Li, Y.; Meng, Y.; Chen, Y.; Wang, X.; Chen, J.; Zhang, Q.; Shao, J.; Zhong, C. Sulforaphane inhibits gastric cancer stem cells via suppressing sonic hedgehog pathway. Int. J. Food Sci. Nutr., 2019, 70(5), 570-578.
[] [PMID: 30624124]
Castro, N.P.; Rangel, M.C.; Merchant, A.S.; MacKinnon, G.; Cuttitta, F.; Salomon, D.S.; Kim, Y.S. Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo. Cancer Prev. Res., 2019, 12(3), 147-158.
[] [PMID: 30679159]
Wang, F.; Sun, Y.; Huang, X.; Qiao, C.; Zhang, W.; Liu, P.; Wang, M. Sulforaphane inhibits self-renewal of lung cancer stem cells through the modulation of sonic Hedgehog signaling pathway and polyhomeotic homolog 3. AMB Express, 2021, 11(1), 121.
[] [PMID: 34424425]
Yao, C.J.; Lai, G.M.; Yeh, C.T.; Lai, M.T.; Shih, P.H.; Chao, W.J.; Whang-Peng, J.; Chuang, S.E.; Lai, T.Y. Honokiol eliminates human oral cancer stem-like cells accompanied with suppression of Wnt/ β -catenin signaling and apoptosis induction. Evidence-based Complement. Altern. Med., 2013, 2013, 2013.
Sengupta, S.; Nagalingam, A.; Muniraj, N.; Bonner, M.Y.; Mistriotis, P.; Afthinos, A.; Kuppusamy, P.; Lanoue, D.; Cho, S.; Korangath, P.; Shriver, M.; Begum, A.; Merino, V.F.; Huang, C-Y.; Arbiser, J.L.; Matsui, W.; Győrffy, B.; Konstantopoulos, K.; Sukumar, S.; Marignani, P.A.; Saxena, N.K.; Sharma, D. Activation of tumor suppressor LKB1 by honokiol abrogates cancer stem-like phenotype in breast cancer via inhibition of oncogenic Stat3. Oncogene, 2017, 36(41), 5709-5721.
[] [PMID: 28581518]
Ashry, R.; Elhussiny, M.; Abdellatif, H.; Elkashty, O.; Abdel-Ghaffar, H.A.; Gaballa, E.T.; Mousa, S.A. Genetic interpretation of the im-pacts of honokiol and EGCG on apoptotic and self-renewal pathways in HEp-2 human laryngeal CD44high cancer stem cells. Nutr. Cancer, 2022, 74(6), 2152-2173.
[PMID: 34590505]
Huang, J.S.; Yao, C.J.; Chuang, S.E.; Yeh, C.T.; Lee, L.M.; Chen, R.M.; Chao, W.J.; Whang-Peng, J.; Lai, G.M. Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction. BMC Cancer, 2016, 16(1), 245.
[] [PMID: 27012679]
Ma, Y.; Yu, W.; Shrivastava, A.; Srivastava, R.K.; Shankar, S. Inhibition of pancreatic cancer stem cell characteristics by α‐Mangostin: Molecular mechanisms involving sonic hedgehog and Nanog. J. Cell. Mol. Med., 2019, 23(4), 2719-2730.
[] [PMID: 30712329]
Chien, H.J.; Ying, T.H.; Hsieh, S.C.; Lin, C.L.; Yu, Y.L.; Kao, S.H.; Hsieh, Y.H. α‐Mangostin attenuates stemness and enhances cisplatin‐induced cell death in cervical cancer stem‐like cells through induction of mitochondrial‐mediated apoptosis. J. Cell. Physiol., 2020, 235(7-8), 5590-5601.
[] [PMID: 31960449]
Verma, R.K.; Yu, W.; Shrivastava, A.; Shankar, S.; Srivastava, R.K. α-Mangostin-encapsulated PLGA nanoparticles inhibit pancreatic carcinogenesis by targeting cancer stem cells in human, and transgenic (KrasG12D, and KrasG12D/tp53R270H) mice. Sci. Rep., 2016, 6(1), 32743.
[] [PMID: 27624879]
Li, Y.W.; Xu, J.; Zhu, G.Y.; Huang, Z.J.; Lu, Y.; Li, X.Q.; Wang, N.; Zhang, F.X. Apigenin suppresses the stem cell-like properties of triple-negative breast cancer cells by inhibiting YAP/TAZ activity. Cell Death Discov., 2018, 4(1), 105.
[] [PMID: 30479839]
Erdogan, S.; Turkekul, K.; Serttas, R.; Erdogan, Z. The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy. Biomed. Pharmacother., 2017, 88, 210-217.
[] [PMID: 28107698]
Kim, B.; Jung, N.; Lee, S.; Sohng, J.K.; Jung, H.J. Apigenin inhibits cancer stem cell-like phenotypes in human glioblastoma cells via sup-pression of c-met signaling. Phytother. Res., 2016, 30(11), 1833-1840.
[] [PMID: 27468969]
Erdogan, S.; Doganlar, O.; Doganlar, Z.B.; Serttas, R.; Turkekul, K.; Dibirdik, I.; Bilir, A. The flavonoid apigenin reduces prostate cancer CD44+ stem cell survival and migration through PI3K/Akt/NF-κB signaling. Life Sci., 2016, 162, 77-86.
[] [PMID: 27569589]
Kim, S.H.; Singh, S.V. Mammary cancer chemoprevention by withaferin A is accompanied by in vivo suppression of self-renewal of can-cer stem cells. Cancer Prev. Res., 2014, 7(7), 738-747.
[] [PMID: 24824039]
Wu, C.H.; Hong, B.H.; Ho, C.T.; Yen, G.C. Targeting cancer stem cells in breast cancer: potential anticancer properties of 6-shogaol and pterostilbene. J. Agric. Food Chem., 2015, 63(9), 2432-2441.
[] [PMID: 25686711]
Liao, K.; Xia, B.; Zhuang, Q.Y.; Hou, M.J.; Zhang, Y.J.; Luo, B.; Qiu, Y.; Gao, Y.F.; Li, X.J.; Chen, H.F.; Ling, W.H.; He, C.Y.; Huang, Y.J.; Lin, Y.C.; Lin, Z.N. Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF-κB/COX-2 pathway. Theranostics, 2015, 5(3), 302-321.
[] [PMID: 25553117]
Soltanian, S.; Riahirad, H.; Pabarja, A.; Jafari, E.; Khandani, B.K. Effect of Cinnamic acid and FOLFOX in diminishing side population and downregulating cancer stem cell markers in colon cancer cell line HT-29. Daru, 2018, 26(1), 19-29.
[] [PMID: 30209760]
Zhen, X.; Choi, H.S.; Kim, J.H.; Kim, S.L.; Liu, R.; Yun, B.S.; Lee, D.S. Machilin D, a lignin derived from Saururus chinensis, suppresses breast cancer stem cells and inhibits NF-κB signaling. Biomolecules, 2020, 10(2), 245.
[] [PMID: 32033472]
Jiang, F.; Li, Y.; Mu, J.; Hu, C.; Zhou, M.; Wang, X.; Si, L.; Ning, S.; Li, Z. Glabridin inhibits cancer stem cell-like properties of human breast cancer cells: An epigenetic regulation of miR-148a/SMAd2 signaling. Mol. Carcinog., 2016, 55(5), 929-940.
[] [PMID: 25980823]
Su, Y.; Huang, W.C.; Lee, W.H.; Bamodu, O.A.; Zucha, M.A.; Astuti, I.; Suwito, H.; Yeh, C.T.; Lin, C.M. Methoxyphenyl chalcone sensi-tizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication. Tumour Biol., 2017, 39(5), 1010428317691689.
[] [PMID: 28466786]
Tiwari, A.; Modi, S.J.; Gabhe, S.Y.; Kulkarni, V.M. Evaluation of piperine against cancer stem cells (CSCs) of hepatocellular carcinoma: Insights into epithelial-mesenchymal transition (EMT). Bioorg. Chem., 2021, 110, 104776.
[] [PMID: 33743225]
Choi, H.; Kim, S.L.; Kim, J.H.; Deng, H.Y.; Yun, B.S.; Lee, D.S. Triterpene acid (3-O-p-coumaroyltormentic acid) isolated from aronia extracts inhibits breast cancer stem cell formation through downregulation of c-Myc protein. Int. J. Mol. Sci., 2018, 19(9), 2528.
[] [PMID: 30149665]
Wang, W.; Zhao, C.; Jou, D.; Lü, J.; Zhang, C.; Lin, L.; Lin, J. Ursolic acid inhibits the growth of colon cancer-initiating cells by targeting STAT3. Anticancer Res., 2013, 33(10), 4279-4284.
[PMID: 24122993]
Mukherjee, S.; Mazumdar, M.; Chakraborty, S.; Manna, A.; Saha, S.; Khan, P.; Bhattacharjee, P.; Guha, D.; Adhikary, A.; Mukhjerjee, S.; Das, T. Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop. Stem Cell Res. Ther., 2014, 5(5), 116.
[] [PMID: 25315241]
Chen, W.; Li, L.; Zhang, X.; Liang, Y.; Pu, Z.; Wang, L.; Mo, J. Curcumin: A calixarene derivative micelle potentiates anti-breast cancer stem cells effects in xenografted, triple-negative breast cancer mouse models. Drug Deliv., 2017, 24(1), 1470-1481.
[] [PMID: 28956452]
Fan, P.; Fan, S.; Wang, H.; Mao, J.; Shi, Y.; Ibrahim, M.M.; Ma, W.; Yu, X.; Hou, Z.; Wang, B.; Li, L. Genistein decreases the breast can-cer stem-like cell population through hedgehog pathway. Stem Cell Res. Ther., 2013, 4(6), 146.
[] [PMID: 24331293]
Huang, W.; Wan, C.; Luo, Q.; Huang, Z.; Luo, Q. Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer. Int. J. Mol. Sci., 2014, 15(3), 3432-3443.
[] [PMID: 24573253]
Sato, A.; Okada, M.; Shibuya, K.; Watanabe, E.; Seino, S.; Suzuki, K.; Narita, Y.; Shibui, S.; Kayama, T.; Kitanaka, C. Resveratrol pro-motes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells. Stem Cell Res., 2013, 11(1), 601-610.
[] [PMID: 23651583]
Qin, T.; Cheng, L.; Xiao, Y.; Qian, W.; Li, J.; Wu, Z.; Wang, Z.; Xu, Q.; Duan, W.; Wong, L.; Wu, E.; Ma, Q.; Ma, J. NAF-1 inhibition by resveratrol suppresses cancer stem cell-like properties and the invasion of pancreatic cancer. Front. Oncol., 2020, 10, 1038.
[] [PMID: 32766132]
Wang, W.J.; Sui, H.; Qi, C.; Li, Q.; Zhang, J.; Wu, S.F.; Mei, M.Z.; Lu, Y.Y.; Wan, Y.T.; Chang, H.; Guo, P.T. Ursolic acid inhibits prolif-eration and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hy-poxia-inducible factor-1α in vitro. Oncol. Rep., 2016, 36(1), 428-440.
[] [PMID: 27221674]
Aliebrahimi, S.; Kouhsari, S.M.; Arab, S.S.; Shadboorestan, A.; Ostad, S.N. Phytochemicals, withaferin A and carnosol, overcome pancre-atic cancer stem cells as c-Met inhibitors. Biomed. Pharmacother., 2018, 106, 1527-1536.
[] [PMID: 30119228]

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