Flavonoid-Based Cancer Therapy: An Updated Review | Bentham Science
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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Review Article

Flavonoid-Based Cancer Therapy: An Updated Review

Author(s): Elham Hosseinzadeh, Ali Hassanzadeh, Faroogh Marofi, Mohammad Reza Alivand and Saeed Solali*

Volume 20, Issue 12, 2020

Page: [1398 - 1414] Pages: 17

DOI: 10.2174/1871520620666200423071759

Price: $65

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Abstract

As cancers are one of the most important causes of human morbidity and mortality worldwide, researchers try to discover novel compounds and therapeutic approaches to decrease survival of cancer cells, angiogenesis, proliferation and metastasis. In the last decade, use of special phytochemical compounds and flavonoids was reported to be an interesting and hopeful tactic in the field of cancer therapy. Flavonoids are natural polyphenols found in plant, fruits, vegetables, teas and medicinal herbs. Based on reports, over 10,000 flavonoids have been detected and categorized into several subclasses, including flavonols, anthocyanins, flavanones, flavones, isoflavones and chalcones. It seems that the anticancer effect of flavonoids is mainly due to their antioxidant and anti inflammatory activities and their potential to modulate molecular targets and signaling pathways involved in cell survival, proliferation, differentiation, migration, angiogenesis and hormone activities. The main aim of this review is to evaluate the relationship between flavonoids consumption and cancer risk, and discuss the anti-cancer effects of these natural compounds in human cancer cells. Hence, we tried to collect and revise important recent in vivo and in vitro researches about the most effective flavonoids and their main mechanisms of action in various types of cancer cells.

Keywords: Flavonoids, cancer, proliferation, angiogenesis, apoptosis, migration.

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]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J. Clin., 2017, 67(1), 7-30.
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]
[3]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[4]
Chakraborty, C.; Sharma, A.R.; Sharma, G.; Sarkar, B.K.; Lee, S-S. The novel strategies for next-generation cancer treatment: miRNA combined with chemotherapeutic agents for the treatment of cancer. Oncotarget, 2018, 9(11), 10164-10174.
[http://dx.doi.org/10.18632/oncotarget.24309] [PMID: 29515800]
[5]
Bhullar, K.S.; Lagarón, N.O.; McGowan, E.M.; Parmar, I.; Jha, A.; Hubbard, B.P.; Rupasinghe, H.P.V. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol. Cancer, 2018, 17(1), 48-48.
[http://dx.doi.org/10.1186/s12943-018-0804-2] [PMID: 29455673]
[6]
Rothwell, J.A.; Knaze, V.; Zamora-Ros, R. Polyphenols: Dietary assessment and role in the prevention of cancers. Curr. Opin. Clin. Nutr. Metab. Care, 2017, 20(6), 512-521.
[http://dx.doi.org/10.1097/MCO.0000000000000424] [PMID: 28915128]
[7]
Le Marchand, L. Cancer preventive effects of flavonoids--a review. Biomed. Pharmacother., 2002, 56(6), 296-301.
[http://dx.doi.org/10.1016/S0753-3322(02)00186-5] [PMID: 12224601]
[8]
Batra, P.; Sharma, A.K. Anti-cancer potential of flavonoids: Recent trends and future perspectives 3 Biotech, 2013, 3(6), 439-459.
[9]
Li, Q.; Yu, H.M.; Meng, X.F.; Lin, J.S.; Li, Y.J.; Hou, B.K. Ectopic expression of glycosyltransferase UGT76E11 increases flavonoid accumulation and enhances abiotic stress tolerance in Arabidopsis. Plant Biol (Stuttg), 2018, 20(1), 10-19.
[http://dx.doi.org/10.1111/plb.12627] [PMID: 28902451]
[10]
Ajmala Shireen, P.; Abdul Mujeeb, V.M.; Muraleedharan, K. Theoretical insights on flavanones as antioxidants and UV filters: A TDDFT and NLMO study. J. Photochem. Photobiol. B, 2017, 170, 286-294.
[http://dx.doi.org/10.1016/j.jphotobiol.2017.04.021] [PMID: 28456119]
[11]
Grabacka, M.M.; Gawin, M.; Pierzchalska, M. Phytochemical modulators of mitochondria: The search for chemopreventive agents and supportive therapeutics. Pharmaceuticals (Basel), 2014, 7(9), 913-942.
[http://dx.doi.org/10.3390/ph7090913] [PMID: 25192192]
[12]
Li, Y.; Zhang, T.; Chen, G.Y. Flavonoids and colorectal cancer prevention. Antioxidants (Basel, Switzerland), 2018, 7(12)
[13]
Zhang, H.; Tsao, R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr. Opin. Food Sci., 2016, 8, 33-42.
[http://dx.doi.org/10.1016/j.cofs.2016.02.002]
[14]
Bartmańska, A.; Tronina, T.; Popłoński, J.; Milczarek, M.; Filip-Psurska, B.; Wietrzyk, J. Highly cancer selective antiproliferative activity of natural prenylated flavonoids. Molecules, 2018, 23(11), E2922.
[http://dx.doi.org/10.3390/molecules23112922] [PMID: 30423918]
[15]
Wang, L.; Lee, I.M.; Zhang, S.M.; Blumberg, J.B.; Buring, J.E.; Sesso, H.D. Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Am. J. Clin. Nutr., 2009, 89(3), 905-912.
[http://dx.doi.org/10.3945/ajcn.2008.26913] [PMID: 19158208]
[16]
Ravishankar, D.; Rajora, A.K.; Greco, F.; Osborn, H.M.I. Flavonoids as prospective compounds for anti-cancer therapy. Int. J. Biochem. Cell Biol., 2013, 45(12), 2821-2831.
[http://dx.doi.org/10.1016/j.biocel.2013.10.004] [PMID: 24128857]
[17]
Wang, Y.Q.; Lu, J.L.; Liang, Y.R.; Li, Q.S. Suppressive effects of EGCG on cervical cancer. Molecules, 2018, 23(9), E2334.
[http://dx.doi.org/10.3390/molecules23092334] [PMID: 30213130]
[18]
Romagnolo, D.F.; Selmin, O.I. Flavonoids and cancer prevention: A review of the evidence. J. Nutr. Gerontol. Geriatr., 2012, 31(3), 206-238.
[http://dx.doi.org/10.1080/21551197.2012.702534] [PMID: 22888839]
[19]
Vue, B.; Zhang, S.; Chen, Q.H. Flavonoids with therapeutic potential in prostate cancer. Anticancer. Agents Med. Chem., 2016, 16(10), 1205-1229.
[http://dx.doi.org/10.2174/1871520615666151008122622] [PMID: 26446382]
[20]
Davatgaran-Taghipour, Y.; Masoomzadeh, S.; Farzaei, M.H.; Bahramsoltani, R.; Karimi-Soureh, Z.; Rahimi, R.; Abdollahi, M. Polyphenol nanoformulations for cancer therapy: Experimental evidence and clinical perspective. Int. J. Nanomedicine, 2017, 12, 2689-2702.
[http://dx.doi.org/10.2147/IJN.S131973]] [PMID: 28435252]
[21]
Abotaleb, M.; Samuel, S.M.; Varghese, E.; Varghese, S.; Kubatka, P.; Liskova, A.; Büsselberg, D. Flavonoids in cancer and apoptosis. Cancers (Basel), 2018, 11(1), E28.
[http://dx.doi.org/10.3390/cancers11010028] [PMID: 30597838]
[22]
Zhang, H.W.; Hu, J.J.; Fu, R.Q.; Liu, X.; Zhang, Y.H.; Li, J.; Liu, L.; Li, Y.N.; Deng, Q.; Luo, Q.S.; Ouyang, Q.; Gao, N. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Sci. Rep., 2018, 8(1), 11255.
[http://dx.doi.org/10.1038/s41598-018-29308-7] [PMID: 30050147]
[23]
Masuelli, L.; Benvenuto, M.; Mattera, R.; Di Stefano, E.; Zago, E.; Taffera, G.; Tresoldi, I.; Giganti, M.G.; Frajese, G.V.; Berardi, G.; Modesti, A.; Bei, R. In vitro and in vivo anti-tumoral effects of the flavonoid apigenin in malignant mesothelioma. Front. Pharmacol., 2017, 8(373), 373.
[http://dx.doi.org/10.3389/fphar.2017.00373] [PMID: 28674496]
[24]
Jennings, A.; MacGregor, A.; Spector, T.; Cassidy, A. Higher dietary flavonoid intakes are associated with lower objectively measured body composition in women: Evidence from discordant monozygotic twins. Am. J. Clin. Nutr., 2017, 105(3), 626-634.
[http://dx.doi.org/10.3945/ajcn.116.144394] [PMID: 28100511]
[25]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal, 2013, 2013., 162750.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[26]
Saraei, R.; Marofi, F.; Naimi, A.; Talebi, M.; Ghaebi, M.; Javan, N.; Salimi, O.; Hassanzadeh, A. Leukemia therapy by flavonoids: Future and involved mechanisms. J. Cell. Physiol., 2019, 234(6), 8203-8220.
[PMID: 30500074]
[27]
Pal, M.; Dakarapu, R.; Parasuraman, K.; Subramanian, V.; Yeleswarapu, K.R. Regio- and stereospecific synthesis of novel 3-enynyl-substituted thioflavones/flavones using a copper-free palladium-catalyzed reaction. J. Org. Chem., 2005, 70(18), 7179-7187.
[http://dx.doi.org/10.1021/jo050828+] [PMID: 16122236]
[28]
Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79(5), 727-747.
[http://dx.doi.org/10.1093/ajcn/79.5.727] [PMID: 15113710]
[29]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci., 2016, 5, e47-e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[30]
Matthies, A.; Clavel, T.; Gütschow, M.; Engst, W.; Haller, D.; Blaut, M.; Braune, A. Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl. Environ. Microbiol., 2008, 74(15), 4847-4852.
[http://dx.doi.org/10.1128/AEM.00555-08] [PMID: 18539813]
[31]
Khan, N.; Afaq, F.; Mukhtar, H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid. Redox Signal., 2008, 10(3), 475-510.
[http://dx.doi.org/10.1089/ars.2007.1740] [PMID: 18154485]
[32]
Lagiou, P.; Samoli, E.; Lagiou, A.; Katsouyanni, K.; Peterson, J.; Dwyer, J.; Trichopoulos, D. Flavonoid intake in relation to lung cancer risk: Case-control study among women in Greece. Nutr. Cancer, 2004, 49(2), 139-143.
[http://dx.doi.org/10.1207/s15327914nc4902_4] [PMID: 15489206]
[33]
Ivey, K.L.; Hodgson, J.M.; Croft, K.D.; Lewis, J.R.; Prince, R.L. Flavonoid intake and all-cause mortality. Am. J. Clin. Nutr., 2015, 101(5), 1012-1020.
[http://dx.doi.org/10.3945/ajcn.113.073106] [PMID: 25832340]
[34]
Wang, Y.; Gapstur, S.M.; Gaudet, M.M.; Peterson, J.J.; Dwyer, J.T.; McCullough, M.L. Evidence for an association of dietary flavonoid intake with breast cancer risk by estrogen receptor status is limited. J. Nutr., 2014, 144(10), 1603-1611.
[http://dx.doi.org/10.3945/jn.114.196964] [PMID: 25143370]
[35]
Geybels, M.S.; Verhage, B.A.; Arts, I.C.; van Schooten, F.J.; Goldbohm, R.A.; van den Brandt, P.A. Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer. Am. J. Epidemiol., 2013, 177(12), 1388-1398.
[http://dx.doi.org/10.1093/aje/kws419] [PMID: 23722011]
[36]
Cassidy, A.; Huang, T.; Rice, M.S.; Rimm, E.B.; Tworoger, S.S. Intake of dietary flavonoids and risk of epithelial ovarian cancer. Am. J. Clin. Nutr., 2014, 100(5), 1344-1351.
[http://dx.doi.org/10.3945/ajcn.114.088708] [PMID: 25332332]
[37]
Woo, H.D.; Kim, J. Dietary flavonoid intake and smoking-related cancer risk: a meta-analysis. PLoS One, 2013, 8(9), e75604.
[http://dx.doi.org/10.1371/journal.pone.0075604] [PMID: 24069431]
[38]
Chang, H.; Lei, L.; Zhou, Y.; Ye, F.; Zhao, G. Dietary flavonoids and the risk of colorectal cancer: An updated meta-analysis of epidemiological studies. Nutrients, 2018, 10(7), E950.
[http://dx.doi.org/10.3390/nu10070950] [PMID: 30041489]
[39]
Sak, K. Epidemiological evidences on dietary flavonoids and breast cancer risk: A narrative review. Asian Pac. J. Cancer Prev., 2017, 18(9), 2309-2328.
[PMID: 28950673]
[40]
Sun, L.; Subar, A.F.; Bosire, C.; Dawsey, S.M.; Kahle, L.L.; Zimmerman, T.P.; Abnet, C.C.; Heller, R.; Graubard, B.I.; Cook, M.B.; Petrick, J.L. Dietary flavonoid intake reduces the risk of head and neck but not esophageal or gastric cancer in US men and women. J. Nutr., 2017, 147(9), 1729-1738.
[PMID: 28724656]
[41]
Zamora-Ros, R.; Barupal, D.K.; Rothwell, J.A.; Jenab, M.; Fedirko, V.; Romieu, I.; Aleksandrova, K.; Overvad, K.; Kyrø, C.; Tjønneland, A.; Affret, A.; His, M.; Boutron-Ruault, M.C.; Katzke, V.; Kühn, T.; Boeing, H.; Trichopoulou, A.; Naska, A.; Kritikou, M.; Saieva, C.; Agnoli, C.; Santucci de Magistris, M.; Tumino, R.; Fasanelli, F.; Weiderpass, E.; Skeie, G.; Merino, S.; Jakszyn, P.; Sánchez, M.J.; Dorronsoro, M.; Navarro, C.; Ardanaz, E.; Sonestedt, E.; Ericson, U.; Maria Nilsson, L.; Bodén, S.; Bueno-de-Mesquita, H.B.; Peeters, P.H.; Perez-Cornago, A.; Wareham, N.J.; Khaw, K.T.; Freisling, H.; Cross, A.J.; Riboli, E.; Scalbert, A. Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort. Int. J. Cancer, 2017, 140(8), 1836-1844.
[http://dx.doi.org/10.1002/ijc.30582] [PMID: 28006847]
[42]
Nimptsch, K.; Zhang, X.; Cassidy, A.; Song, M.; O’Reilly, É.J.; Lin, J.H.; Pischon, T.; Rimm, E.B.; Willett, W.C.; Fuchs, C.S.; Ogino, S.; Chan, A.T.; Giovannucci, E.L.; Wu, K. Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts. Am. J. Clin. Nutr., 2016, 103(1), 184-191.
[http://dx.doi.org/10.3945/ajcn.115.117507] [PMID: 26537935]
[43]
Reale, G.; Russo, G.I.; Di Mauro, M.; Regis, F.; Campisi, D.; Giudice, A.L.; Marranzano, M.; Ragusa, R.; Castelli, T.; Cimino, S.; Morgia, G. Association between dietary flavonoids intake and prostate cancer risk: A case-control study in Sicily. Complement. Ther. Med., 2018, 39, 14-18.
[http://dx.doi.org/10.1016/j.ctim.2018.05.002] [PMID: 30012385]
[44]
Russo, G.I.; Campisi, D.; Di Mauro, M.; Regis, F.; Reale, G.; Marranzano, M.; Ragusa, R.; Solinas, T.; Madonia, M.; Cimino, S.; Morgia, G. Dietary consumption of phenolic acids and prostate cancer: A case-control study in sicily, Southern Italy. Molecules, 2017, 22(12), E2159.
[http://dx.doi.org/10.3390/molecules22122159] [PMID: 29206164]
[45]
Messina, M. Impact of soy foods on the development of breast cancer and the prognosis of breast cancer patients. Forschende Komplementarmedizin, 2016, 23(2), 75-80.
[46]
Lagiou, P.; Rossi, M.; Lagiou, A.; Tzonou, A.; La Vecchia, C.; Trichopoulos, D. Flavonoid intake and liver cancer: A case-control study in Greece. Cancer Causes Control, 2008, 19(8), 813-818.
[http://dx.doi.org/10.1007/s10552-008-9144-7] [PMID: 18350370]
[47]
Woo, H.D.; Kim, J. Dietary flavonoid intake and risk of stomach and colorectal cancer. World J. Gastroenterol., 2013, 19(7), 1011-1019.
[http://dx.doi.org/10.3748/wjg.v19.i7.1011] [PMID: 23467443]
[48]
Mursu, J.; Nurmi, T.; Tuomainen, T.P.; Salonen, J.T.; Pukkala, E.; Voutilainen, S. Intake of flavonoids and risk of cancer in Finnish men: The Kuopio Ischaemic heart disease risk factor study. Int. J. Cancer, 2008, 123(3), 660-663.
[http://dx.doi.org/10.1002/ijc.23421] [PMID: 18338754]
[49]
Grosso, G. Effects of polyphenol-rich foods on human health. Nutrients, 2018, 10(8), E1089.
[http://dx.doi.org/10.3390/nu10081089] [PMID: 30110959]
[50]
Zamora-Ros, R.; Biessy, C.; Rothwell, J.A.; Monge, A.; Lajous, M.; Scalbert, A.; López-Ridaura, R.; Romieu, I. Dietary polyphenol intake and their major food sources in the Mexican Teachers’. Cohort. Br. J. Nutr., 2018, 120(3), 353-360.
[http://dx.doi.org/10.1017/S0007114518001381] [PMID: 29860950]
[51]
Hassanzadeh, A.; Naimi, A.; Hagh, M.F.; Saraei, R.; Marofi, F.; Solali, S. Kaempferol improves TRAIL-Mediated apoptosis in leukemia MOLT-4 cells by inhibition of anti-apoptotic proteins and promotion of death receptors expression. Anticancer. Agents Med. Chem., 2019, 19(15), 1835-1845.
[http://dx.doi.org/10.2174/1871520619666190731155859] [PMID: 31364517]
[52]
Lee, H.S.; Cho, H.J.; Kwon, G.T.; Park, J.H. Kaempferol downregulates insulin-like growth factor-I receptor and ErbB3 signaling in HT-29 human colon cancer cells. J. Cancer Prev., 2014, 19(3), 161-169.
[http://dx.doi.org/10.15430/JCP.2014.19.3.161] [PMID: 25337585]
[53]
Dey, N.; Williams, C.; Leyland-Jones, B.; De, P. A critical role for HER3 in HER2-amplified and non-amplified breast cancers: Function of a kinase-dead RTK. Am. J. Transl. Res., 2015, 7(4), 733-750.
[PMID: 26064441]
[54]
Sullivan, K.D.; Palaniappan, V.V.; Espinosa, J.M. ATM regulates cell fate choice upon p53 activation by modulating mitochondrial turnover and ROS levels. Cell Cycle, 2015, 14(1), 56-63.
[http://dx.doi.org/10.4161/15384101.2014.973330] [PMID: 25483068]
[55]
Lee, C.F.; Yang, J.S.; Tsai, F.J.; Chiang, N.N.; Lu, C.C.; Huang, Y.S.; Chen, C.; Chen, F.A. Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells. Int. J. Oncol., 2016, 48(5), 2007-2014.
[http://dx.doi.org/10.3892/ijo.2016.3420]] [PMID: 26984266]
[56]
Xie, F.; Su, M.; Qiu, W.; Zhang, M.; Guo, Z.; Su, B.; Liu, J.; Li, X.; Zhou, L. Kaempferol promotes apoptosis in human bladder cancer cells by inducing the tumor suppressor, PTEN. Int. J. Mol. Sci., 2013, 14(11), 21215-21226.
[http://dx.doi.org/10.3390/ijms141121215] [PMID: 24284390]
[57]
Hopkins, B.D.; Hodakoski, C.; Barrows, D.; Mense, S.M.; Parsons, R.E. PTEN function: The long and the short of it. Trends Biochem. Sci., 2014, 39(4), 183-190.
[http://dx.doi.org/10.1016/j.tibs.2014.02.006] [PMID: 24656806]
[58]
Song, M.S.; Salmena, L.; Pandolfi, P.P. The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell Biol., 2012, 13(5), 283-296.
[http://dx.doi.org/10.1038/nrm3330] [PMID: 22473468]
[59]
Jo, E.; Park, S.J.; Choi, Y.S.; Jeon, W.K.; Kim, B.C. Kaempferol suppresses transforming growth factor-β1-induced epithelial-to mesenchymal transition and migration of A549 lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at threonine-179. Neoplasia, 2015, 17(7), 525-537.
[http://dx.doi.org/10.1016/j.neo.2015.06.004] [PMID: 26297431]
[60]
Yao, K.; Chen, H.; Liu, K.; Langfald, A.; Yang, G.; Zhang, Y.; Yu, D.H.; Kim, M.O.; Lee, M.H.; Li, H.; Bae, K.B.; Kim, H.G.; Ma, W.Y.; Bode, A.M.; Dong, Z.; Dong, Z. Kaempferol targets RSK2 and MSK1 to suppress UV radiation-induced skin cancer. Cancer Prev. Res. (Phila.), 2014, 7(9), 958-967.
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0126] [PMID: 24994661]
[61]
Ortega-Martínez, S. A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis. Front. Mol. Neurosci., 2015, 8, 46-46.
[http://dx.doi.org/10.3389/fnmol.2015.00046] [PMID: 26379491]
[62]
Siegelin, M.D.; Reuss, D.E.; Habel, A.; Herold-Mende, C.; von Deimling, A. The flavonoid kaempferol sensitizes human glioma cells to TRAIL-mediated apoptosis by proteasomal degradation of survivin. Mol. Cancer Ther., 2008, 7(11), 3566-3574.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0236] [PMID: 19001439]
[63]
Mylonis, I.; Lakka, A.; Tsakalof, A.; Simos, G. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions. Biochem. Biophys. Res. Commun., 2010, 398(1), 74-78.
[http://dx.doi.org/10.1016/j.bbrc.2010.06.038] [PMID: 20558139]
[64]
Kim, S.H.; Choi, K.C. Anti-cancer effect and underlying mechanism(s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxicol. Res., 2013, 29(4), 229-234.
[http://dx.doi.org/10.5487/TR.2013.29.4.229] [PMID: 24578792]
[65]
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]
[66]
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.
[67]
Sevrioukova, I.F. Apoptosis-inducing factor: Structure, function, and redox regulation. Antioxid. Redox Signal., 2011, 14(12), 2545-2579.
[http://dx.doi.org/10.1089/ars.2010.3445]] [PMID: 20868295]
[68]
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]
[69]
Tang, X.J.; Huang, K.M.; Gui, H.; Wang, J.J.; Lu, J.T.; Dai, L.J.; Zhang, L.; Wang, G. Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells. Int. J. Nanomedicine, 2016, 11, 4991-5002.
[http://dx.doi.org/10.2147/IJN.S114302] [PMID: 27757032]
[70]
Pan, H.; Hu, Q.; Wang, J.; Liu, Z.; Wu, D.; Lu, W.; Huang, J. Myricetin is a novel inhibitor of human inosine 5′-monophosphate dehydrogenase with anti-leukemia activity. Biochem. Biophys. Res. Commun., 2016, 477(4), 915-922.
[http://dx.doi.org/10.1016/j.bbrc.2016.06.158] [PMID: 27378425]
[71]
Woo, S.M.; Choi, Y.K.; Kim, A.J.; Cho, S.G.; Ko, S.G. p53 causes buteinmediated apoptosis of chronic myeloid leukemia cells. Mol. Med. Rep., 2016, 13(2), 1091-1096.
[http://dx.doi.org/10.3892/mmr.2015.4672] [PMID: 26676515]
[72]
Choi, H.S.; Kim, M.K.; Choi, Y.K.; Shin, Y.C.; Cho, S.G.; Ko, S.G. Rhus verniciflua Stokes (RVS) and butein induce apoptosis of paclitaxel-resistant SKOV-3/PAX ovarian cancer cells through inhibition of AKT phosphorylation. BMC Complement. Altern. Med., 2016, 16, 122.
[http://dx.doi.org/10.1186/s12906-016-1103-3] [PMID: 27121110]
[73]
Tang, Y.L.; Huang, L.B.; Lin, W.H.; Wang, L.N.; Tian, Y.; Shi, D.; Wang, J.; Qin, G.; Li, A.; Liang, Y.N.; Zhou, H.J.; Ke, Z.Y.; Huang, W.; Deng, W.; Luo, X.Q. Butein inhibits cell proliferation and induces cell cycle arrest in acute lymphoblastic leukemia via FOXO3a/p27kip1 pathway. Oncotarget, 2016, 7(14), 18651-18664.
[http://dx.doi.org/10.18632/oncotarget.7624] [PMID: 26919107]
[74]
Klotz, L.O.; Sánchez-Ramos, C.; Prieto-Arroyo, I.; Urbánek, P.; Steinbrenner, H.; Monsalve, M. Redox regulation of FoxO transcription factors. Redox Biol., 2015, 6, 51-72.
[http://dx.doi.org/10.1016/j.redox.2015.06.019] [PMID: 26184557]
[75]
Chua, A.W.L.; Hay, H.S.; Rajendran, P.; Shanmugam, M.K.; Li, F.; Bist, P.; Koay, E.S.C.; Lim, L.H.K.; Kumar, A.P.; Sethi, G. Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-κB activation in breast and pancreatic tumor cells. Biochem. Pharmacol., 2010, 80(10), 1553-1562.
[http://dx.doi.org/10.1016/j.bcp.2010.07.045]] [PMID: 20699088]
[76]
Liu, S.C.; Chen, C.; Chung, C.H.; Wang, P.C.; Wu, N.L.; Cheng, J.K.; Lai, Y.W.; Sun, H.L.; Peng, C.Y.; Tang, C.H.; Wang, S.W. Inhibitory effects of butein on cancer metastasis and bioenergetic modulation. J. Agric. Food Chem., 2014, 62(37), 9109-9117.
[http://dx.doi.org/10.1021/jf502370c] [PMID: 25137351]
[77]
Lai, Y.W.; Wang, S.W.; Chang, C.H.; Liu, S.C.; Chen, Y.J.; Chi, C.W.; Chiu, L.P.; Chen, S.S.; Chiu, A.W.; Chung, C.H. Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulation. BMC Complement. Altern. Med., 2015, 15, 445.
[http://dx.doi.org/10.1186/s12906-015-0970-3] [PMID: 26694191]
[78]
Yang, P.Y.; Hu, D.N.; Lin, I.C.; Liu, F.S. Butein shows cytotoxic effects and induces apoptosis in human ovarian cancer cells. Am. J. Chin. Med., 2015, 43(4), 769-782.
[http://dx.doi.org/10.1142/S0192415X15500482] [PMID: 26119952]
[79]
Gasparini, C.; Vecchi Brumatti, L.; Monasta, L.; Zauli, G. TRAIL-based therapeutic approaches for the treatment of pediatric malignancies. Curr. Med. Chem., 2013, 20(17), 2254-2271.
[http://dx.doi.org/10.2174/0929867311320170009] [PMID: 23458616]
[80]
Almasan, A.; Ashkenazi, A. Apo2L/TRAIL: Apoptosis signaling, biology, and potential for cancer therapy. Cytokine Growth Factor Rev., 2003, 14(3-4), 337-348.
[http://dx.doi.org/10.1016/S1359-6101(03)00029-7] [PMID: 12787570]
[81]
Hassanzadeh, A.; Farshdousti Hagh, M.; Alivand, M.R.; Akbari, A.A.M.; Shams Asenjan, K.; Saraei, R.; Solali, S. Down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL. J. Cell. Physiol., 2018, 233(10), 6470-6485.
[http://dx.doi.org/10.1002/jcp.26585] [PMID: 29741767]
[82]
Baruah, M.M.; Khandwekar, A.P.; Sharma, N. Quercetin modulates Wnt signaling components in prostate cancer cell line by inhibiting cell viability, migration, and metastases. Tumour Biol., 2016, 37(10), 14025-14034.
[http://dx.doi.org/10.1007/s13277-016-5277-6] [PMID: 27495232]
[83]
Lan, H.; Hong, W.; Fan, P.; Qian, D.; Zhu, J.; Bai, B. Quercetin inhibits cell migration and invasion in human osteosarcoma cells. Internat. J. Experim. Cell. Physiol. Biochem. Pharmacol., 2017, 43(2), 553-567.
[84]
Atashpour, S.; Fouladdel, S.; Movahhed, T.K.; Barzegar, E.; Ghahremani, M.H.; Ostad, S.N.; Azizi, E. Quercetin induces cell cycle arrest and apoptosis in CD133(+) cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin. Iran. J. Basic Med. Sci., 2015, 18(7), 635-643.
[PMID: 26351552]
[85]
Srivastava, S.; Somasagara, R.R.; Hegde, M.; Nishana, M.; Tadi, S.K.; Srivastava, M.; Choudhary, B.; Raghavan, S.C. Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci. Rep., 2016, 6, 24049.
[http://dx.doi.org/10.1038/srep24049] [PMID: 27068577]
[86]
Gao, X.; Wang, B.; Wei, X.; Men, K.; Zheng, F.; Zhou, Y.; Zheng, Y.; Gou, M.; Huang, M.; Guo, G.; Huang, N.; Qian, Z.; Wei, Y. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer. Nanoscale, 2012, 4(22), 7021-7030.
[http://dx.doi.org/10.1039/c2nr32181e] [PMID: 23044718]
[87]
Nguyen, L.T.; Lee, Y.H.; Sharma, A.R.; Park, J.B.; Jagga, S.; Sharma, G.; Lee, S.S.; Nam, J.S. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity. Korean J. Physiol. Pharmacol., 2017, 21(2), 205-213.
[http://dx.doi.org/10.4196/kjpp.2017.21.2.205] [PMID: 28280414]
[88]
Xiang, T.; Fang, Y.; Wang, S.X. Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway. J. Huazhong Univ. Sci. Technol., 2014, 34(5), 740-744.
[89]
Han, M.; Song, Y.; Zhang, X. Quercetin suppresses the migration and invasion in human colon cancer Caco-2 cells through regulating toll-like receptor 4/nuclear factor-kappa B pathway. Pharmacogn. Mag., 2016, 12(Suppl. 2), S237-S244.
[http://dx.doi.org/10.4103/0973-1296.182154] [PMID: 27279714]
[90]
Kim, J.H.; Kim, M.J.; Choi, K.C.; Son, J. Quercetin sensitizes pancreatic cancer cells to TRAIL-induced apoptosis through JNK-mediated cFLIP turnover. Int. J. Biochem. Cell Biol., 2016, 78, 327-334.
[http://dx.doi.org/10.1016/j.biocel.2016.07.033] [PMID: 27477310]
[91]
Shen, X.; Si, Y.; Wang, Z.; Wang, J.; Guo, Y.; Zhang, X. Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling. Int. J. Mol. Med., 2016, 38(2), 619-626.
[http://dx.doi.org/10.3892/ijmm.2016.2625] [PMID: 27278820]
[92]
Mukherjee, A.; Khuda-Bukhsh, A.R. Quercetin down-regulates IL-6/STAT-3 signals to induce mitochondrial-mediated apoptosis in a nonsmall- cell lung-cancer cell line, A549. J. Pharmacopuncture, 2015, 18(1), 19-26.
[http://dx.doi.org/10.3831/KPI.2015.18.002] [PMID: 25830055]
[93]
Sonoki, H.; Sato, T.; Endo, S.; Matsunaga, T.; Yamaguchi, M.; Yamazaki, Y.; Sugatani, J.; Ikari, A. Quercetin decreases claudin-2 expression mediated by up-regulation of microRNA miR-16 in lung adenocarcinoma A549 cells. Nutrients, 2015, 7(6), 4578-4592.
[http://dx.doi.org/10.3390/nu7064578] [PMID: 26061016]
[94]
Maurya, A.K.; Vinayak, M. Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and Protein Kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol. Biol. Rep., 2015, 42(9), 1419-1429.
[http://dx.doi.org/10.1007/s11033-015-3921-7] [PMID: 26311153]
[95]
Zhao, Q.; Chen, X.Y.; Martin, C. Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants. Sci. Bull. (Beijing), 2016, 61(18), 1391-1398.
[http://dx.doi.org/10.1007/s11434-016-1136-5] [PMID: 27730005]
[96]
Li, H.L.; Zhang, S.; Wang, Y.; Liang, R.R.; Li, J.; An, P.; Wang, Z.M.; Yang, J.; Li, Z.F. Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells. Mol. Med. Rep., 2013, 7(1), 266-270.
[http://dx.doi.org/10.3892/mmr.2012.1123] [PMID: 23064738]
[97]
Jiang, L.; Song, H.; Guo, H.; Wang, C.; Lu, Z. Baicalein inhibits proliferation and migration of bladder cancer cell line T24 by down-regulation of microRNA-106. Biomed. Pharmacother., 2018, 107, 1583-1590.
[98]
Liu, H.; Dong, Y.; Gao, Y.; Du, Z.; Wang, Y.; Cheng, P.; Chen, A.; Huang, H. The fascinating effects of baicalein on cancer: A review. Int. J. Mol. Sci., 2016, 17(10), 1681.
[http://dx.doi.org/10.3390/ijms17101681] [PMID: 27735841]
[99]
Donald, G.; Hertzer, K.; Eibl, G. Baicalein--an intriguing therapeutic phytochemical in pancreatic cancer. Curr. Drug Targets, 2012, 13(14), 1772-1776.
[http://dx.doi.org/10.2174/138945012804545470] [PMID: 23140288]
[100]
Cathcart, M-C.; Useckaite, Z.; Drakeford, C.; Semik, V.; Lysaght, J.; Gately, K.; O’Byrne, K.J.; Pidgeon, G.P. Anti-cancer effects of baicalein in non-small cell lung cancer in vitro and in vivo. BMC Cancer, 2016, 16(1), 707.
[http://dx.doi.org/10.1186/s12885-016-2740-0] [PMID: 27586635]
[101]
Chen, Z.; Hou, R.; Gao, S.; Song, D.; Feng, Y. Baicalein inhibits proliferation activity of human colorectal cancer cells HCT116 through downregulation of ezrin. Int. J. Experim. Cell. Physiol. Biochem. Pharmacol., 2018, 49(5), 2035-2046.
[102]
Rouven Brückner, B.; Pietuch, A.; Nehls, S.; Rother, J.; Janshoff, A. Ezrin is a major regulator of membrane tension in epithelial cells. Sci. Rep., 2015, 5, 14700.
[http://dx.doi.org/10.1038/srep14700] [PMID: 26435322]
[103]
Rayees Ahmad, M.; Girija Sastry, V.; Bano, N.; Anwar, S. Synthesis of novel chalcone derivatives by conventional and microwave irradiation methods and their pharmacological activities. Arab. J. Chem., 2016, 9, S931-S935.
[http://dx.doi.org/10.1016/j.arabjc.2011.09.002]
[104]
Mahapatra, D.K.; Bharti, S.K.; Asati, V. Anti-cancer chalcones: Structural and molecular target perspectives. Eur. J. Med. Chem., 2015, 98, 69-114.
[http://dx.doi.org/10.1016/j.ejmech.2015.05.004] [PMID: 26005917]
[105]
Pedrini, F.S.; Chiaradia, L.D.; Licínio, M.A.; de Moraes, A.C.; Curta, J.C.; Costa, A.; Mascarello, A.; Creczinsky-Pasa, T.B.; Nunes, R.J.; Yunes, R.A.; Santos-Silva, M.C. Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic leukaemia cells by (2E)-3-(2-naphthyl)-1-(3′-methoxy-4′-hydroxy-phenyl)-2-propen-1-one. J. Pharm. Pharmacol., 2010, 62(9), 1128-1136.
[http://dx.doi.org/10.1111/j.2042-7158.2010.01141.x] [PMID: 20796191]
[106]
Pande, A.N.; Biswas, S.; Reddy, N.D.; Jayashree, B.S.; Kumar, N.; Rao, C.M. In vitro and in vivo anticancer studies of 2′-hydroxy chalcone derivatives exhibit apoptosis in colon cancer cells by HDAC inhibition and cell cycle arrest. EXCLI J., 2017, 16, 448-463.
[PMID: 28694750]
[107]
Das, M.; Manna, K. Chalcone scaffold in anticancer armamentarium: A molecular insight. J. Toxicol., 2016, 2016, 7651047-7651047.
[http://dx.doi.org/10.1155/2016/7651047] [PMID: 26880913]
[108]
Kim, B.H.; Park, K.C.; Park, J.H.; Lee, C.G.; Ye, S.K.; Park, J.Y. Inhibition of tyrosinase activity and melanin production by the chalcone derivative 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone. Biochem. Biophys. Res. Commun., 2016, 480(4), 648-654.
[http://dx.doi.org/10.1016/j.bbrc.2016.10.110] [PMID: 27983977]
[109]
Tuerxuntayi, A.; Liu, Y.Q.; Tulake, A.; Kabas, M.; Eblimit, A.; Aisa, H.A. Kaliziri extract upregulates tyrosinase, TRP-1, TRP-2 and MITF expression in murine B16 melanoma cells. BMC Complement. Altern. Med., 2014, 14, 166-166.
[http://dx.doi.org/10.1186/1472-6882-14-166] [PMID: 24884952]
[110]
Ji, Y.; Jia, L.; Zhang, Y.; Xing, Y.; Wu, X.; Zhao, B.; Zhang, D.; Xu, X.; Qiao, X. Antitumor activity of the plant extract morin in tongue squamous cell carcinoma cells. Oncol. Rep., 2018, 40(5), 3024-3032.
[http://dx.doi.org/10.3892/or.2018.6650] [PMID: 30132559]
[111]
Li, B.; Jin, X.; Meng, H.; Hu, B.; Zhang, T.; Yu, J.; Chen, S.; Guo, X.; Wang, W.; Jiang, W.; Wang, J. Morin promotes prostate cancer cells chemosensitivity to paclitaxel through miR-155/GATA3 axis. Oncotarget, 2017, 8(29), 47849-47860.
[http://dx.doi.org/10.18632/oncotarget.18133] [PMID: 28599307]
[112]
Perumal, N.; Perumal, M.; Kannan, A.; Subramani, K.; Halagowder, D.; Sivasithamparam, N. Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells. Exp. Cell Res., 2017, 355(2), 124-141.
[http://dx.doi.org/10.1016/j.yexcr.2017.03.062] [PMID: 28366538]
[113]
Meng, Z.; Moroishi, T.; Guan, K-L. Mechanisms of Hippo pathway regulation. Genes Dev., 2016, 30(1), 1-17.
[http://dx.doi.org/10.1101/gad.274027.115] [PMID: 26728553]
[114]
Shin, S.S.; Won, S.Y.; Noh, D.H.; Hwang, B.; Kim, W.J.; Moon, S.K. Morin inhibits proliferation, migration, and invasion of bladder cancer EJ cells via modulation of signaling pathways, cell cycle regulators, and transcription factor-mediated MMP-9 expression. Drug Dev. Res., 2017, 78(2), 81-90.
[http://dx.doi.org/10.1002/ddr.21377] [PMID: 28176369]
[115]
Li, H.W.; Zou, T.B.; Jia, Q.; Xia, E.Q.; Cao, W.J.; Liu, W.; He, T.P.; Wang, Q. Anticancer effects of morin-7-sulphate sodium, a flavonoid derivative, in mouse melanoma cells. Biomed. Pharmacother., 2016, 84, 909-916.
[116]
Cui, S.; Wang, J.; Wu, Q.; Qian, J.; Yang, C.; Bo, P. Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways. Oncotarget, 2017, 8(13), 21674-21691.
[http://dx.doi.org/10.18632/oncotarget.15535] [PMID: 28423510]
[117]
Tai, Y.L.; Chen, L.C.; Shen, T.L. Emerging roles of focal adhesion kinase in cancer. BioMed Res. Int., 2015, 2015, 690690.
[http://dx.doi.org/10.1155/2015/690690] [PMID: 25918719]
[118]
Zhang, J.; Su, H.; Li, Q.; Li, J.; Zhao, Q. Genistein decreases A549 cell viability via inhibition of the PI3K/AKT/HIF1α/VEGF and NFκB/COX2 signaling pathways. Mol. Med. Rep., 2017, 15(4), 2296-2302.
[http://dx.doi.org/10.3892/mmr.2017.6260] [PMID: 28259980]
[119]
Shafiee, G.; Saidijam, M.; Tavilani, H.; Ghasemkhani, N.; Khodadadi, I. Genistein induces apoptosis and inhibits proliferation of HT29 colon cancer cells. Int. J. Mol. Cell. Med., 2016, 5(3), 178-191.
[PMID: 27942504]
[120]
Ma, C.H.; Zhang, Y.X.; Tang, L.H.; Yang, X.J.; Cui, W.M.; Han, C.C.; Ji, W.Y. MicroRNA-1469, a p53-responsive microRNA promotes Genistein induced apoptosis by targeting Mcl1 in human laryngeal cancer cells. Biomed. Pharmacother., 2018, 106, 665-671.
[121]
Sanaei, M.; Kavoosi, F.; Roustazadeh, A.; Golestan, F. Effect of genistein in comparison with trichostatin A on reactivation of DNMTs genes in hepatocellular carcinoma. J. Clin. Transl. Hepatol., 2018, 6(2), 141-146.
[http://dx.doi.org/10.14218/JCTH.2018.00002] [PMID: 29951358]
[122]
Kim, J.K.; Samaranayake, M.; Pradhan, S. Epigenetic mechanisms in mammals. Cell. Mol. Life Sci., 2009, 66(4), 596-612.
[http://dx.doi.org/10.1007/s00018-008-8432-4] [PMID: 18985277]
[123]
Zhou, P.; Wang, C.; Hu, Z.; Chen, W.; Qi, W.; Li, A. Genistein induces apoptosis of colon cancer cells by reversal of epithelial-to-mesenchymal via a Notch1/NF-κB/slug/E-cadherin pathway. BMC Cancer, 2017, 17(1), 813.
[http://dx.doi.org/10.1186/s12885-017-3829-9] [PMID: 29202800]
[124]
Li, W.; Gao, F.; Ma, X.; Wang, R.; Dong, X.; Wang, W. Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis. Oncotarget, 2017, 8(20), 32586-32599.
[http://dx.doi.org/10.18632/oncotarget.15937] [PMID: 28427230]
[125]
Yan, B.; Zhao, D.; Yao, Y.; Bao, Z.; Lu, G.; Zhou, J. Deguelin induces the apoptosis of lung squamous cell carcinoma cells through regulating the expression of galectin-1. Int. J. Biol. Sci., 2016, 12(7), 850-860.
[http://dx.doi.org/10.7150/ijbs.14773] [PMID: 27313498]
[126]
Robles, A.J.; Cai, S.; Cichewicz, R.H.; Mooberry, S.L. Selective activity of deguelin identifies therapeutic targets for androgen receptor-positive breast cancer. Breast Cancer Res. Treat., 2016, 157(3), 475-488.
[http://dx.doi.org/10.1007/s10549-016-3841-9] [PMID: 27255535]
[127]
Zhao, H.; Jiao, Y.; Zhang, Z. Deguelin inhibits the migration and invasion of lung cancer A549 and H460 cells via regulating actin cytoskeleton rearrangement. Int. J. Clin. Exp. Pathol., 2015, 8(12), 15582-15590.
[PMID: 26884827]
[128]
Zheng, W.; Lu, S.; Cai, H.; Kang, M.; Qin, W.; Li, C.; Wu, Y. Deguelin inhibits proliferation and migration of human pancreatic cancer cells in vitro targeting hedgehog pathway. Oncol. Lett., 2016, 12(4), 2761-2765.
[http://dx.doi.org/10.3892/ol.2016.4928] [PMID: 27698853]
[129]
Gupta, S.; Takebe, N.; Lorusso, P. Targeting the Hedgehog pathway in cancer. Ther. Adv. Med. Oncol., 2010, 2(4), 237-250.
[http://dx.doi.org/10.1177/1758834010366430] [PMID: 21789137]
[130]
Thamilselvan, V.; Menon, M.; Thamilselvan, S. Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway. Int. J. Cancer, 2011, 129(12), 2916-2927.
[http://dx.doi.org/10.1002/ijc.25949] [PMID: 21472727]
[131]
Kang, W.; Zheng, X.; Wang, P.; Guo, S. Deguelin exerts anticancer activity of human gastric cancer MGC-803 and MKN-45 cells in vitro. Int. J. Mol. Med., 2018, 41(6), 3157-3166.
[http://dx.doi.org/10.3892/ijmm.2018.3532] [PMID: 29512685]
[132]
Yan, X.; Qi, M.; Li, P.; Zhan, Y.; Shao, H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci., 2017, 7, 50.
[http://dx.doi.org/10.1186/s13578-017-0179-x] [PMID: 29034071]
[133]
Madunić, J.; Madunić, I.V.; Gajski, G.; Popić, J.; Garaj-Vrhovac, V. Apigenin: A dietary flavonoid with diverse anticancer properties. Cancer Lett., 2018, 413, 11-22.
[http://dx.doi.org/10.1016/j.canlet.2017.10.041] [PMID: 29097249]
[134]
Wu, D-G.; Yu, P.; Li, J-W.; Jiang, P.; Sun, J.; Wang, H-Z.; Zhang, L-D.; Wen, M-B.; Bie, P. Apigenin potentiates the growth inhibitory effects by IKK-β-mediated NF-κB activation in pancreatic cancer cells. Toxicol. Lett., 2014, 224(1), 157-164.
[135]
Xu, M.; Wang, S.; Song, Y.; Yao, J.; Huang, K.; Zhu, X. Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/β-catenin signaling pathway. Oncol. Lett., 2016, 11(5), 3075-3080.
[136]
Sung, B.; Chung, H.Y.; Kim, N.D. Role of apigenin in cancer prevention via the induction of apoptosis and autophagy. J. Cancer Prev., 2016, 21(4), 216-226.
[http://dx.doi.org/10.15430/JCP.2016.21.4.216] [PMID: 28053955]
[137]
Shukla, S.; Fu, P.; Gupta, S. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosis: Int. J. Programmed Cell Death, 2014, 19(5), 883-894.
[138]
Budhraja, A.; Gao, N.; Zhang, Z.; Son, Y.O.; Cheng, S.; Wang, X.; Ding, S.; Hitron, A.; Chen, G.; Luo, J.; Shi, X. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol. Cancer Ther., 2012, 11(1), 132-142.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0343] [PMID: 22084167]
[139]
Gupta, S.; Afaq, F.; Mukhtar, H. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene, 2002, 21(23), 3727-3738.
[http://dx.doi.org/10.1038/sj.onc.1205474] [PMID: 12032841]
[140]
Cao, X.; Liu, B.; Cao, W.; Zhang, W.; Zhang, F.; Zhao, H.; Meng, R.; Zhang, L.; Niu, R.; Hao, X.; Zhang, B. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells. Chinese J. Cancer Res., 2013, 25(2), 212-222.
[141]
Zhou, Z.; Tang, M.; Liu, Y.; Zhang, Z.; Lu, R.; Lu, J. Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line. Anticancer Drugs, 2017, 28(4), 446-456.
[http://dx.doi.org/10.1097/CAD.0000000000000479] [PMID: 28125432]
[142]
Dai, J.; Van Wie, P.G.; Fai, L.Y.; Kim, D.; Wang, L.; Poyil, P.; Luo, J.; Zhang, Z. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells. Toxicol. Appl. Pharmacol., 2016, 311, 106-112.
[http://dx.doi.org/10.1016/j.taap.2016.09.016] [PMID: 27664007]
[143]
Ahn, J.; Sanz-Moreno, V.; Marshall, C.J. The metastasis gene NEDD9 product acts through integrin β3 and Src to promote mesenchymal motility and inhibit amoeboid motility. J. Cell Sci., 2012, 125(Pt 7), 1814-1826.
[http://dx.doi.org/10.1242/jcs.101444] [PMID: 22328516]
[144]
Smith, M.L.; Murphy, K.; Doucette, C.D.; Greenshields, A.L.; Hoskin, D.W. The dietary flavonoid fisetin causes cell cycle arrest, caspase-dependent apoptosis, and enhanced cytotoxicity of chemotherapeutic drugs in triple-negative breast cancer cells. J. Cell. Biochem., 2016, 117(8), 1913-1925.
[http://dx.doi.org/10.1002/jcb.25490] [PMID: 26755433]
[145]
Youns, M.; Abdel Halim Hegazy, W. The natural flavonoid fisetin inhibits cellular proliferation of hepatic, colorectal, and pancreatic cancer cells through modulation of multiple signaling pathways. PLoS One, 2017, 12(1), e0169335.
[http://dx.doi.org/10.1371/journal.pone.0169335] [PMID: 28052097]
[146]
Sundarraj, K.; Raghunath, A.; Perumal, E. A review on the chemotherapeutic potential of fisetin: In vitro evidences. Biomed. Pharmacother., 2018, 97, 928-940.
[http://dx.doi.org/10.1016/j.biopha.2017.10.164] [PMID: 29136771]
[147]
Suh, Y.; Afaq, F.; Johnson, J.J.; Mukhtar, H. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways. Carcinogenesis, 2009, 30(2), 300-307.
[http://dx.doi.org/10.1093/carcin/bgn269] [PMID: 19037088]
[148]
Lim, D.Y.; Park, J.H. Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 296(5), G1060-G1068.
[http://dx.doi.org/10.1152/ajpgi.90490.2008] [PMID: 19264955]
[149]
Hartman, M.L.; Czyz, M. MITF in melanoma: Mechanisms behind its expression and activity. Cell. Mol. Life Sci., 2015, 72(7), 1249-1260.
[http://dx.doi.org/10.1007/s00018-014-1791-0] [PMID: 25433395]
[150]
Hartman, M.L.; Czyz, M. Pro-survival role of MITF in melanoma. J. Invest. Dermatol., 2015, 135(2), 352-358.
[http://dx.doi.org/10.1038/jid.2014.319] [PMID: 25142731]
[151]
Wang, X.; Bai, H.; Zhang, X.; Liu, J.; Cao, P.; Liao, N.; Zhang, W.; Wang, Z.; Hai, C. Inhibitory effect of oleanolic acid on hepatocellular carcinoma via ERK-p53-mediated cell cycle arrest and mitochondrial-dependent apoptosis. Carcinogenesis, 2013, 34(6), 1323-1330.
[http://dx.doi.org/10.1093/carcin/bgt058] [PMID: 23404993]
[152]
Zhao, X.; Liu, M.; Li, D. Oleanolic acid suppresses the proliferation of lung carcinoma cells by miR-122/Cyclin G1/MEF2D axis. Mol. Cell. Biochem., 2015, 400(1-2), 1-7.
[http://dx.doi.org/10.1007/s11010-014-2228-7] [PMID: 25472877]
[153]
He, W.M.; Yin, J.Q.; Cheng, X.D.; Lu, X.; Ni, L.; Xi, Y.; Yin, G.D.; Lu, G.Y.; Sun, W.; Wei, M.G. Oleanolic acid attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells. BMC Complement. Altern. Med., 2018, 18(1), 205.
[http://dx.doi.org/10.1186/s12906-018-2265-y] [PMID: 29973206]
[154]
Ashour, A.; El-Sharkawy, S.; Amer, M.; Abdel Bar, F.; Katakura, Y.; Miyamoto, T.; Toyota, N.; Bang, T.H.; Kondo, R.; Shimizu, K. Rational design and synthesis of topoisomerase I and II inhibitors based on oleanolic acid moiety for new anti-cancer drugs. Bioorg. Med. Chem., 2014, 22(1), 211-220.
[http://dx.doi.org/10.1016/j.bmc.2013.11.034] [PMID: 24326278]
[155]
McClendon, A.K.; Osheroff, N. DNA topoisomerase II, genotoxicity, and cancer. Mutat. Res., 2007, 623(1-2), 83-97.
[http://dx.doi.org/10.1016/j.mrfmmm.2007.06.009] [PMID: 17681352]
[156]
Rui, L.X.; Shu, S.Y.; Jun, W.J.; Mo, C.Z.; Wu, S.Z.; Min, L.S.; Yuan, L.; Yong, P.J.; Cheng, S.Z.; Sheng, W.S.; Yao, T.Z. The dual induction of apoptosis and autophagy by SZC014, a synthetic oleanolic acid derivative, in gastric cancer cells via NF-κB pathway. Tumour Biol., 2016, 37(4), 5133-5144.
[157]
Žiberna, L.; Šamec, D.; Mocan, A.; Nabavi, S.F.; Bishayee, A.; Farooqi, A.A.; Sureda, A.; Nabavi, S.M. Oleanolic acid alters multiple cell signaling pathways: Implication in cancer prevention and therapy. Int. J. Mol. Sci., 2017, 18(3), 643.
[http://dx.doi.org/10.3390/ijms18030643] [PMID: 28300756]
[158]
Liu, J.; Wu, N.; Ma, L.; Zhong, J-T.; Liu, G.; Zheng, L-H.; Lin, X. p38 MAPK signaling mediates mitochondrial apoptosis in cancer cells induced by oleanolic acid. Asian Pac. J. Cancer Prev., 2014, 15(11), 4519-4525.
[159]
Li, L.; Lin, J.; Sun, G.; Wei, L.; Shen, A.; Zhang, M.; Peng, J. Oleanolic acid inhibits colorectal cancer angiogenesis in vivo and in vitro via suppression of STAT3 and Hedgehog pathways. Mol. Med. Rep., 2016, 13(6), 5276-5282.
[http://dx.doi.org/10.3892/mmr.2016.5171] [PMID: 27108756]
[160]
Banjerdpongchai, R.; Wudtiwai, B.; Khawon, P. Induction of human hepatocellular carcinoma HepG2 cell apoptosis by naringin. Asian Pac. J. Cancer Prev., 2016, 17(7), 3289-3294.
[PMID: 27509965]
[161]
Wang, H.; Xu, Y.S.; Wang, M.L.; Cheng, C.; Bian, R.; Yuan, H.; Wang, Y.; Guo, T.; Zhu, L.L.; Zhou, H. Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: Implications for the treatment of neurodegenerative disorders. Int. J. Mol. Med., 2017, 39(4), 819-830.
[http://dx.doi.org/10.3892/ijmm.2017.2904] [PMID: 28260042]
[162]
Li, J.; Dong, Y.; Hao, G.; Wang, B.; Wang, J.; Liang, Y.; Liu, Y.; Zhen, E.; Feng, D.; Liang, G. Naringin suppresses the development of glioblastoma by inhibiting FAK activity. J. Drug Target., 2017, 25(1), 41-48.
[http://dx.doi.org/10.1080/1061186X.2016.1184668]] [PMID: 27125297]
[163]
Zhao, J.; Pestell, R.; Guan, J.L. Transcriptional activation of cyclin D1 promoter by FAK contributes to cell cycle progression. Mol. Biol. Cell, 2001, 12(12), 4066-4077.
[http://dx.doi.org/10.1091/mbc.12.12.4066] [PMID: 11739801]
[164]
Yoshinaga, A.; Kajiya, N.; Oishi, K.; Kamada, Y.; Ikeda, A.; Chigwechokha, P.K.; Kibe, T.; Kishida, M.; Kishida, S.; Komatsu, M.; Shiozaki, K. NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation. Eur. J. Pharmacol., 2016, 782, 21-29.
[http://dx.doi.org/10.1016/j.ejphar.2016.04.035] [PMID: 27105818]
[165]
Aroui, S.; Aouey, B.; Chtourou, Y.; Meunier, A.C.; Fetoui, H.; Kenani, A. Naringin suppresses cell metastasis and the expression of matrix metalloproteinases (MMP-2 and MMP-9) via the inhibition of ERK-P38-JNK signaling pathway in human glioblastoma. Chem. Biol. Interact., 2016, 244, 195-203.
[http://dx.doi.org/10.1016/j.cbi.2015.12.011] [PMID: 26721195]
[166]
Guo, B.; Zhang, Y.; Hui, Q.; Wang, H.; Tao, K. Naringin suppresses the metabolism of A375 cells by inhibiting the phosphorylation of c-Src. Tumour Biol., 2016, 37(3), 3841-3850.
[http://dx.doi.org/10.1007/s13277-015-4235-z] [PMID: 26476533]
[167]
Aroui, S.; Najlaoui, F.; Chtourou, Y.; Meunier, A.C.; Laajimi, A.; Kenani, A.; Fetoui, H. Naringin inhibits the invasion and migration of human glioblastoma cell via downregulation of MMP-2 and MMP-9 expression and inactivation of p38 signaling pathway. Tumour Biol., 2016, 37(3), 3831-3839.
[http://dx.doi.org/10.1007/s13277-015-4230-4] [PMID: 26474590]
[168]
Zeng, L.; Zhen, Y.; Chen, Y.; Zou, L.; Zhang, Y.; Hu, F.; Feng, J.; Shen, J.; Wei, B. Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF-κB/COX-2-caspase-1 pathway in HeLa cervical cancer cells. Int. J. Oncol., 2014, 45(5), 1929-1936.
[http://dx.doi.org/10.3892/ijo.2014.2617] [PMID: 25174821]
[169]
Li, H.; Yang, B.; Huang, J.; Xiang, T.; Yin, X.; Wan, J.; Luo, F.; Zhang, L.; Li, H.; Ren, G. Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway. Toxicol. Lett., 2013, 220(3), 219-228.
[http://dx.doi.org/10.1016/j.toxlet.2013.05.006] [PMID: 23694763]

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