Login Register Cart 0
Generic placeholder image

Current Drug Research Reviews

Editor-in-Chief

ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Mini-Review Article

A Review on Anticancer Profile of Flavonoids: Sources, Chemistry, Mechanisms, Structure-activity Relationship and Anticancer Activity

Author(s): Suprava Shah, Rakesh Narang, Vikram Jeet Singh, Govindaiah Pilli and Surendra Kumar Nayak*

Volume 15, Issue 2, 2023

Published on: 20 February, 2023

Page: [122 - 148] Pages: 27

DOI: 10.2174/2589977515666230120144852

Price: $65

Abstract

Background: Epidemiological studies have suggested that a regular intake of flavonoids is beneficial for cellular homeostasis and in the prevention of the transformation of normal cells into cancerous cells. Because of their multiple biological targets, flavonoids have been studied and investigated as phytoconstituents with potential anticancer properties. Flavonoids interfere in the development of cancerous cells by inhibition of topoisomerases, protein kinases, angiogenesis, induction of apoptosis, cell cycle arrest, modulation of multidrug resistance, and improvement in anti-oxidative activities. The current review summarizes the anticancer properties of flavonoids along with the key structural features and their mechanisms. The present study provides a detailed analysis of anticancer activities with previously published data on different flavonoids. The review highlighted the structural aspects and mechanism of action of flavonoids with their potential target sites. Flavonoids induce anticancer activity by protein kinases inhibition, P-gp modulation, antiangiogenesis, topoisomerases inhibition, etc. Open ring C, the double bond between C2-C3, the oxo group at C4, and the position of ring B are crucial determinants for their anticancer activity. Flavonoids act by multiple mechanisms but further studies on target selectivity and specificity of flavonoids are necessary to establish them as anticancer therapeutics. The presence of a C2-C3 double bond and oxo group at C4 (also known as an enone moiety) or -OH in the neighbour of a double bond that can transform easily into an enone are common features present in flavonoids. Thus, it can be concluded that enone moiety or its precursor groups are mainly responsible for the anticancer activities of flavonoids via different mechanisms of action.

« Previous Next »
Graphical Abstract

[1]
Ossio R, Roldán-Marín R, Martínez-Said H, Adams DJ, Robles-Espinoza CD. Melanoma: a global perspective. Nat Rev Cancer 2017; 17(7): 393-4.
[http://dx.doi.org/10.1038/nrc.2017.43] [PMID: 28450704]
[2]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, 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]
[3]
Sharma N, Dobhal MP, Joshi YC, Chahar MK. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev 2011; 5(9): 1-12.
[http://dx.doi.org/10.4103/0973-7847.79093] [PMID: 22096313]
[4]
López-Lázaro M. Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anticancer Agents 2002; 2(6): 691-714.
[http://dx.doi.org/10.2174/1568011023353714] [PMID: 12678721]
[5]
Yao H, Xu W, Shi X, Zhang Z. Dietary flavonoids as cancer prevention agents. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2011; 29(1): 1-31.
[http://dx.doi.org/10.1080/10590501.2011.551317] [PMID: 21424974]
[6]
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014; 8(16): 122-46.
[http://dx.doi.org/10.4103/0973-7847.134247] [PMID: 25125885]
[7]
Rodríguez APG. Management of the adverse effects of lenalidomide in multiple myeloma. Adv Ther 2011; 28 (Suppl. 1): 1-10.
[http://dx.doi.org/10.1007/s12325-010-0104-8] [PMID: 21431626]
[8]
Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical review: Serious adverse events associated with the use of rituximab - a critical care perspective. Crit Care 2012; 16(4): 231.
[http://dx.doi.org/10.1186/cc11304] [PMID: 22967460]
[9]
Riccio G, Coppola C, Piscopo G, et al. Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I from Type II cardiomyopathies? Hum Vaccin Immunother 2016; 12(5): 1124-31.
[http://dx.doi.org/10.1080/21645515.2015.1125056] [PMID: 26836985]
[10]
Taugourdeau-Raymond S, Rouby F, Default A, Jean-Pastor MJ. Bevacizumab-induced serious side-effects: a review of the French pharma-covigilance database. Eur J Clin Pharmacol 2012; 68(7): 1103-7.
[http://dx.doi.org/10.1007/s00228-012-1232-7] [PMID: 22349162]
[11]
Bence AK, Adams VR, Piascik P. Pegfilgrastim: a new therapy to prevent neutropenic fever. J Am Pharm Assoc 2002; 42(5): 806-8.
[http://dx.doi.org/10.1331/108658002764653595] [PMID: 12269716]
[12]
Frampton JE, Lee CR, Faulds D. Filgrastim. Drugs 1994; 48(5): 731-60.
[http://dx.doi.org/10.2165/00003495-199448050-00007] [PMID: 7530630]
[13]
Scott LJ. Nivolumab: a review in advanced melanoma. Drugs 2015; 75(12): 1413-24.
[http://dx.doi.org/10.1007/s40265-015-0442-6] [PMID: 26220912]
[14]
Cameron F, Sanford M. Ibrutinib: first global approval. Drugs 2014; 74(2): 263-71.
[http://dx.doi.org/10.1007/s40265-014-0178-8] [PMID: 24464309]
[15]
Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372(21): 2018-28.
[http://dx.doi.org/10.1056/NEJMoa1501824] [PMID: 25891174]
[16]
Gupta AK, Sharma S, Dahiya N, Brashier DBS. Palbociclib: A breakthrough in breast carcinoma in women. Med J Armed Forces India 2016; 72 (Suppl. 1): S37-42.
[http://dx.doi.org/10.1016/j.mjafi.2015.11.002] [PMID: 28050067]
[17]
Richardson PG, Mitsiades C, Hideshima T, Anderson KC. Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu Rev Med 2006; 57(1): 33-47.
[http://dx.doi.org/10.1146/annurev.med.57.042905.122625] [PMID: 16409135]
[18]
da Rocha A, Lopes RM, Schwartsmann G. Natural products in anticancer therapy. Curr Opin Pharmacol 2001; 1(4): 364-9.
[http://dx.doi.org/10.1016/S1471-4892(01)00063-7] [PMID: 11710734]
[19]
Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 2015; 14(2): 111-29.
[http://dx.doi.org/10.1038/nrd4510] [PMID: 25614221]
[20]
Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74(4): 418-25.
[http://dx.doi.org/10.1093/ajcn/74.4.418] [PMID: 11566638]
[21]
Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: Promising anticancer agents. Med Res Rev 2003; 23(4): 519-34.
[http://dx.doi.org/10.1002/med.10033] [PMID: 12710022]
[22]
Lee ER, Kang GH, Cho SG. Effect of flavonoids on human health: old subjects but new challenges. Recent Pat Biotechnol 2007; 1(2): 139-50.
[http://dx.doi.org/10.2174/187220807780809445] [PMID: 19075837]
[23]
Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. Curr Opin Plant Biol 2002; 5(3): 218-23.
[http://dx.doi.org/10.1016/S1369-5266(02)00256-X] [PMID: 11960739]
[24]
Horváthová K, Vachálková A, Novotný L. Flavonoids as chemoprotective agents in civilization diseases. Neoplasma 2001; 48(6): 435-41.
[PMID: 11949833]
[25]
Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci 2016; 5: e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[26]
Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 2013; 3(6): 439-59.
[27]
Guthrie N, Carroll KK. Inhibition of mammary cancer by citrus flavonoids. Adv Exp Med Biol 1998; 439: 227-36.
[http://dx.doi.org/10.1007/978-1-4615-5335-9_16] [PMID: 9781306]
[28]
Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005; 280(7): 5636-45.
[http://dx.doi.org/10.1074/jbc.M408177200] [PMID: 15533929]
[29]
Menezes JCJMDS, Orlikova B, Morceau F, Diederich M. Natural and synthetic flavonoids: structure-activity relationship and chemothera-peutic potential for the treatment of leukemia. Crit Rev Food Sci Nutr 2016; 56 (Suppl. 1): S4-S28.
[http://dx.doi.org/10.1080/10408398.2015.1074532] [PMID: 26463658]
[30]
Brandi ML. Flavonoids: biochemical effects and therapeutic applications. Bone Miner 1992; 19 (Suppl. 1): S3-S14.
[http://dx.doi.org/10.1016/0169-6009(92)90861-7] [PMID: 1422318]
[31]
Seelinger G, Merfort I, Wölfle U, Schempp C. Anti-carcinogenic effects of the flavonoid luteolin. Molecules 2008; 13(10): 2628-51.
[http://dx.doi.org/10.3390/molecules13102628] [PMID: 18946424]
[32]
Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids: Old and new aspects of a class of natural therapeutic drugs. Life Sci 1999; 65(4): 337-53.
[http://dx.doi.org/10.1016/S0024-3205(99)00120-4] [PMID: 10421421]
[33]
Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J 2013; 2013: 1-16.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[34]
Raffa D, Maggio B, Raimondi MV, Plescia F, Daidone G. Recent discoveries of anticancer flavonoids. Eur J Med Chem 2017; 142: 213-28.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.034] [PMID: 28793973]
[35]
Viskupicova J, Ondrejovic M, Sturdik E. Bioavailability and metabolism of flavonoids. J Food Nutr Res 2008; 47(4): 151-62.
[36]
Aherne SA, O’Brien NM. Dietary flavonols: chemistry, food content, and metabolism. Nutrition 2002; 18(1): 75-81.
[http://dx.doi.org/10.1016/S0899-9007(01)00695-5] [PMID: 11827770]
[37]
Prasad S, Phromnoi K, Yadav V, Chaturvedi M, Aggarwal B. Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer. Planta Med 2010; 76(11): 1044-63.
[http://dx.doi.org/10.1055/s-0030-1250111] [PMID: 20635307]
[38]
Koes RE, Quattrocchio F, Mol JNM. The flavonoid biosynthetic pathway in plants: Function and evolution. BioEssays 1994; 16(2): 123-32.
[http://dx.doi.org/10.1002/bies.950160209]
[39]
Velíšek J, Davídek J, Cejpek K. Biosynthesis of food constituents: Natural pigments. Part 2 – a review. Czech J Food Sci 2008; 26(2): 73-98.
[http://dx.doi.org/10.17221/2463-CJFS]
[40]
Qiao L, Sun Y, Chen R, et al. Sonochemical effects on 14 flavonoids common in citrus: relation to stability. PLoS One 2014; 9(2): e87766.
[http://dx.doi.org/10.1371/journal.pone.0087766] [PMID: 24516562]
[41]
Wu X, Zhao Y, Haytowitz DB, Chen P, Pehrsson PR. Effects of domestic cooking on flavonoids in broccoli and calculation of retention factors. Heliyon 2019; 5(3): e01310.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01310] [PMID: 30899833]
[42]
Chaaban H, Ioannou I, Chebil L, et al. Effect of heat processing on thermal stability and antioxidant activity of six flavonoids. J Food Process Preserv 2017; 41(5): e13203.
[http://dx.doi.org/10.1111/jfpp.13203]
[43]
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]
[44]
Williamson G, Kay CD, Crozier A. The bioavailability, transport, and bioactivity of dietary flavonoids: A review from a historical perspec-tive. Compr Rev Food Sci Food Saf 2018; 17(5): 1054-112.
[http://dx.doi.org/10.1111/1541-4337.12351] [PMID: 33350159]
[45]
Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002; 13(10): 572-84.
[http://dx.doi.org/10.1016/S0955-2863(02)00208-5] [PMID: 12550068]
[46]
Park E-J, Pezzuto JM. Flavonoids in cancer prevention. Anticancer Agents Med Chem 2012; 12(8): 836-51.
[http://dx.doi.org/10.2174/187152012802650075] [PMID: 22292763]
[47]
Nishiumi S, Miyamoto S, Kawabata K, et al. Dietary flavonoids as cancer-preventive and therapeutic biofactors. Front Biosci 2011; S3(1): 1332-62.
[http://dx.doi.org/10.2741/229] [PMID: 21622274]
[48]
Cazarolli L, Zanatta L, Alberton E, et al. Flavonoids: prospective drug candidates. Mini Rev Med Chem 2008; 8(13): 1429-40.
[http://dx.doi.org/10.2174/138955708786369564] [PMID: 18991758]
[49]
Lampe JW. Interindividual differences in response to plant-based diets: implications for cancer risk. Am J Clin Nutr 2009; 89(5): 1553S-7S.
[http://dx.doi.org/10.3945/ajcn.2009.26736D] [PMID: 19297461]
[50]
Genoux E, Nicolle E, Boumendjel A. Flavonoids as anticancer agents: recent progress and state of the art? Curr Org Chem 2011; 15(15): 2608-15.
[http://dx.doi.org/10.2174/138527211796367363]
[51]
Lesterhuis WJ, Punt CJA, Hato SV, et al. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J Clin Invest 2011; 121(8): 3100-8.
[http://dx.doi.org/10.1172/JCI43656] [PMID: 21765211]
[52]
Wanderley CW, Colón DF, Luiz JPM, et al. Paclitaxel reduces tumor growth by reprogramming tumor-associated macrophages to an M1 profile in a TLR4-dependent manner. Cancer Res 2018; 78(20): 5891-900.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3480] [PMID: 30104241]
[53]
Baldo BA, Pagani M. Adverse events to nontargeted and targeted chemotherapeutic agents: emphasis on hypersensitivity responses. Immunol Allergy Clin North Am 2014; 34(3): 565-96. viii.
[http://dx.doi.org/10.1016/j.iac.2014.04.003] [PMID: 25017678]
[54]
Hosseinzade A, Sadeghi O, Naghdipour Biregani A, Soukhtehzari S, Brandt GS, Esmaillzadeh A. Immunomodulatory effects of flavonoids: possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity. Front Immunol 2019; 10: 51.
[http://dx.doi.org/10.3389/fimmu.2019.00051] [PMID: 30766532]
[55]
Benavente-García O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem 2008; 56(15): 6185-205.
[http://dx.doi.org/10.1021/jf8006568] [PMID: 18593176]
[56]
Kale A, Gawande S, Kotwal S. Cancer phytotherapeutics: role for flavonoids at the cellular level. Phytother Res 2008; 22(5): 567-77.
[http://dx.doi.org/10.1002/ptr.2283] [PMID: 18398903]
[57]
Walle T. Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? Semin Cancer Biol 2007; 17(5): 354-62.
[http://dx.doi.org/10.1016/j.semcancer.2007.05.002] [PMID: 17574860]
[58]
Ravishankar D, Rajora AK, Greco F, Osborn HMI. Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol 2013; 45(12): 2821-31.
[http://dx.doi.org/10.1016/j.biocel.2013.10.004] [PMID: 24128857]
[59]
Hou DX, Kumamoto T. Flavonoids as protein kinase inhibitors for cancer chemoprevention: direct binding and molecular modeling. Antioxid Redox Signal 2010; 13(5): 691-719.
[http://dx.doi.org/10.1089/ars.2009.2816] [PMID: 20070239]
[60]
Hu R, Kong ANT. Activation of MAP kinases, apoptosis and nutrigenomics of gene expression elicited by dietary cancer-prevention compounds. Nutrition 2004; 20(1): 83-8.
[http://dx.doi.org/10.1016/j.nut.2003.09.015] [PMID: 14698020]
[61]
Powis G. Signalling pathways as target for anticancer drug development. Pharmacol Ther 1994; 62(1-2): 57-95.
[http://dx.doi.org/10.1016/0163-7258(94)90005-1] [PMID: 7991648]
[62]
Geahlen RL, Koonchanok NM, McLaughlin JL, Pratt DE. Inhibition of protein-tyrosine kinase activity by flavanoids and related compounds. J Nat Prod 1989; 52(5): 982-6.
[http://dx.doi.org/10.1021/np50065a011] [PMID: 2607357]
[63]
Constantinou A, Kiguchi K, Huberman E. Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res 1990; 50(9): 2618-24.
[PMID: 2158395]
[64]
Kandaswami C, Lee L-T, Lee P-PH, et al. The antitumor activities of flavonoids. In vivo 2005; 19(5): 895-909.
[PMID: 16097445]
[65]
Ferriola PC, Cody V, Middleton E Jr. Protein kinase C inhibition by plant flavonoids. Biochem Pharmacol 1989; 38(10): 1617-24.
[http://dx.doi.org/10.1016/0006-2952(89)90309-2] [PMID: 2730676]
[66]
Agullo G, Gamet-Payrastre L, Manenti S, et al. Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: A comparison with tyrosine kinase and protein kinase C inhibition. Biochem Pharmacol 1997; 53(11): 1649-57.
[http://dx.doi.org/10.1016/S0006-2952(97)82453-7] [PMID: 9264317]
[67]
Gamet-Payrastre L, Manenti S, Gratacap MP, Tulliez J, Chap H, Payrastre B. Flavonoids and the inhibition of PKC and PI 3-kinase. Gen Pharmacol 1999; 32(3): 279-86.
[http://dx.doi.org/10.1016/S0306-3623(98)00220-1] [PMID: 10211581]
[68]
Pines J. Cyclins and cyclin-dependent kinases: a biochemical view. Biochem J 1995; 308(3): 697-711.
[http://dx.doi.org/10.1042/bj3080697] [PMID: 8948422]
[69]
Kürbitz C, Heise D, Redmer T, et al. Epicatechin gallate and catechin gallate are superior to epigallocatechin gallate in growth suppression and anti-inflammatory activities in pancreatic tumor cells. Cancer Sci 2011; 102(4): 728-34.
[http://dx.doi.org/10.1111/j.1349-7006.2011.01870.x] [PMID: 21241417]
[70]
Han Y, Chen R, Zhao F. Docking analysis of some flavanols as Cdk-4 inhibitor as a possible option to treat retinoblastoma. Biomed Res (Aligarh) 2017; 28(3): 1453-7.
[71]
Zhang J, Zhang L, Xu Y, Jiang S, Shao Y. Deciphering the binding behavior of flavonoids to the cyclin dependent kinase 6/cyclin D complex. PLoS One 2018; 13(5): e0196651.
[http://dx.doi.org/10.1371/journal.pone.0196651] [PMID: 29715320]
[72]
Pan MH, Chen W-J, Lin-Shiau S-Y, Ho CT, Lin JK. Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating inhibitors p21 and p27 in human colorectal carcinoma cells. Carcinogenesis 2002; 23(10): 1677-84.
[http://dx.doi.org/10.1093/carcin/23.10.1677] [PMID: 12376477]
[73]
Shapiro AB, Ling V. Effect of quercetin on hoechst 33342 transport by purified and reconstituted p-glycoprotein. Biochem Pharmacol 1997; 53(4): 587-96.
[http://dx.doi.org/10.1016/S0006-2952(96)00826-X] [PMID: 9105411]
[74]
Jean S, Kiger AA. Classes of phosphoinositide 3-kinases at a glance. J Cell Sci 2014; 127(5): 923-8.
[http://dx.doi.org/10.1242/jcs.093773] [PMID: 24587488]
[75]
Kramer IM. Signal transduction. 3rd ed.; San Diego: Academic Press 2015.
[76]
Tiosano D, Baris HN, Chen A, et al. Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction. PLoS Genet 2019; 15(4): e1008088.
[http://dx.doi.org/10.1371/journal.pgen.1008088] [PMID: 31034465]
[77]
Sabbah DA, Vennerstrom JL, Zhong H. Docking studies on isoformspecific inhibition of phosphoinositide-3-kinases. J Chem Inf Model 2010; 50(10): 1887-98.
[http://dx.doi.org/10.1021/ci1002679] [PMID: 20866085]
[78]
Zhang HW, Hu JJ, Fu RQ, et al. 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]
[79]
Auerbach R, Lewis R, Shinners B, Kubai L, Akhtar N. Angiogenesis assays: a critical overview. Clin Chem 2003; 49(1): 32-40.
[http://dx.doi.org/10.1373/49.1.32] [PMID: 12507958]
[80]
Fresco P, Borges F, Diniz C, Marques MPM. New insights on the anticancer properties of dietary polyphenols. Med Res Rev 2006; 26(6): 747-66.
[http://dx.doi.org/10.1002/med.20060] [PMID: 16710860]
[81]
Tosetti F, Ferrari N, De Flora S, Albini A. ‘Angioprevention’: angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 2002; 16(1): 2-14.
[http://dx.doi.org/10.1096/fj.01-0300rev] [PMID: 11772931]
[82]
Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 1993; 90(7): 2690-4.
[http://dx.doi.org/10.1073/pnas.90.7.2690] [PMID: 7681986]
[83]
Fotsis T, Pepper MS, Aktas E, et al. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 1997; 57(14): 2916-21.
[PMID: 9230201]
[84]
Cao Y, Cao R. Angiogenesis inhibited by drinking tea. Nature 1999; 398(6726): 381.
[http://dx.doi.org/10.1038/18793] [PMID: 10201368]
[85]
Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets 2008; 8(7): 634-46.
[http://dx.doi.org/10.2174/156800908786241050] [PMID: 18991571]
[86]
Fang J, Zhou Q, Liu LZ, et al. Apigenin inhibits tumor angiogenesis through decreasing HIF-1 and VEGF expression. Carcinogenesis 2006; 28(4): 858-64.
[http://dx.doi.org/10.1093/carcin/bgl205] [PMID: 17071632]
[87]
Ansó E, Zuazo A, Irigoyen M, Urdaci MC, Rouzaut A, Martínez-Irujo JJ. Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism. Biochem Pharmacol 2010; 79(11): 1600-9.
[http://dx.doi.org/10.1016/j.bcp.2010.02.004] [PMID: 20153296]
[88]
Pepper MS, Hazel SJ, Hümpel M, Schleuning WD. 8-prenylnaringenin, a novel phytoestrogen, inhibits angiogenesis in vitro and in vivo. J Cell Physiol 2004; 199(1): 98-107.
[http://dx.doi.org/10.1002/jcp.10460] [PMID: 14978739]
[89]
Dolečková I, Rárová L, Grúz J, Vondrusová M, Strnad M, Kryštof V. Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chloroform extract of Orthosiphon stamineus leaves. Fitoterapia 2012; 83(6): 1000-7.
[http://dx.doi.org/10.1016/j.fitote.2012.06.002] [PMID: 22698713]
[90]
Zhang B, Liu L, Zhao S, Wang X, Liu L, Li S. Vitexicarpin acts as a novel angiogenesis inhibitor and its target network. Evid Based Complement Alternat Med 2013; 2013: 1-13.
[http://dx.doi.org/10.1155/2013/278405] [PMID: 23476684]
[91]
Rajesh G, Harshala S, Dhananjay G, Jadhav A, Vikram G. Effect of hydroxyl substitution of flavone on angiogenesis and free radical scavenging activities: A structure–activity relationship studies using computational tools. Eur J Pharm Sci 2010; 39(1-3): 37-44.
[http://dx.doi.org/10.1016/j.ejps.2009.10.008] [PMID: 19874890]
[92]
Guruvayoor C. Girija Kuttan. Antiangiogenic effect of rutin and its regulatory effect on the production of VEGF, IL-1β and TNF-α in tumor associated macrophages. J Biol Sci (Faisalabad, Pak) 2007; 7(8): 1511-9.
[http://dx.doi.org/10.3923/jbs.2007.1511.1519]
[93]
Yamauchi K, Mitsunaga T, Afroze SH, Uddin MN. Structure-activity relationships of methylquercetin on anti-migration and anti-proliferation activity in B16 melanoma cells. Anticancer Res 2017; 37(4): 1575-9.
[http://dx.doi.org/10.21873/anticanres.11487] [PMID: 28373417]
[94]
Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci 2020; 21(9): 3233.
[http://dx.doi.org/10.3390/ijms21093233] [PMID: 32370233]
[95]
Ferté J, Kühnel JM, Chapuis G, Rolland Y, Lewin G, Schwaller MA. Flavonoid-related modulators of multidrug resistance: synthesis, pharmacological activity, and structure-activity relationships. J Med Chem 1999; 42(3): 478-89.
[http://dx.doi.org/10.1021/jm981064b] [PMID: 9986718]
[96]
Di Pietro A, Conseil G, Pérez-Victoria JM, et al. Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Cell Mol Life Sci 2002; 59(2): 307-22.
[http://dx.doi.org/10.1007/s00018-002-8424-8] [PMID: 11915946]
[97]
Critchfield JW, Welsh CJ, Phang JM, Chao Yeh G. Modulation of adriamycin® accumulation and efflux by flavonoids in HCT-15 colon cells. Biochem Pharmacol 1994; 48(7): 1437-45.
[http://dx.doi.org/10.1016/0006-2952(94)90568-1] [PMID: 7945444]
[98]
Scambia G, Ranelletti FO, Panici PB, et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breastcancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol 1994; 34(6): 459-64.
[http://dx.doi.org/10.1007/BF00685655] [PMID: 7923555]
[99]
Chieli E, Romiti N, Cervelli F, Tongiani R. Effects of flavonols on Pglycoprotein activity in cultured rat hepatocytes. Life Sci 1995; 57(19): 1741-51.
[http://dx.doi.org/10.1016/0024-3205(95)02152-9] [PMID: 7475916]
[100]
Mohana S, Ganesan M, Agilan B, et al. Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer. Mol Biosyst 2016; 12(8): 2458-70.
[http://dx.doi.org/10.1039/C6MB00187D] [PMID: 27216424]
[101]
Iriti M, Kubina R, Cochis A, et al. Rutin, a quercetin glycoside, restores chemosensitivity in human breast cancer cells. Phytother Res 2017; 31(10): 1529-38.
[http://dx.doi.org/10.1002/ptr.5878] [PMID: 28752532]
[102]
Hadjeri M, Barbier M, Ronot X, Mariotte AM, Boumendjel A, Boutonnat J. Modulation of P-glycoprotein-mediated multidrug resistance by flavonoid derivatives and analogues. J Med Chem 2003; 46(11): 2125-31.
[http://dx.doi.org/10.1021/jm021099i] [PMID: 12747785]
[103]
Boumendjel A, Di Pietro A, Dumontet C, Barron D. Recent advances in the discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein responsible for cancer cell multidrug resistance. Med Res Rev 2002; 22(5): 512-29.
[http://dx.doi.org/10.1002/med.10015] [PMID: 12210557]
[104]
Martinez-Perez C, Ward C, Cook G, et al. Novel flavonoids as anticancer agents: mechanisms of action and promise for their potential application in breast cancer. Biochem Soc Trans 2014; 42(4): 1017-23.
[http://dx.doi.org/10.1042/BST20140073] [PMID: 25109996]
[105]
Carrington EM, Zhan Y, Brady JL, et al. Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo. Cell Death Differ 2017; 24(5): 878-88.
[http://dx.doi.org/10.1038/cdd.2017.30] [PMID: 28362427]
[106]
Shukla S, Gupta S. Molecular targets for apigenin-induced cell cycle arrest and apoptosis in prostate cancer cell xenograft. Mol Cancer Ther 2006; 5(4): 843-52.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0370] [PMID: 16648554]
[107]
Zhang Q, Zhao XH, Wang ZJ. Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol 2008; 46(6): 2042-53.
[http://dx.doi.org/10.1016/j.fct.2008.01.049] [PMID: 18331776]
[108]
Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci Biotechnol Biochem 2000; 64(9): 1813-20.
[http://dx.doi.org/10.1271/bbb.64.1813] [PMID: 11055382]
[109]
Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem 2007; 18(7): 427-42.
[http://dx.doi.org/10.1016/j.jnutbio.2006.11.004] [PMID: 17321735]
[110]
Kim JH, Kang JW, Kim MS, et al. The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells. Toxicol In vitro 2012; 26(1): 67-73.
[http://dx.doi.org/10.1016/j.tiv.2011.10.012] [PMID: 22056764]
[111]
Pandey P, Khan F, Alzahrani FA, Qari HA, Oves M. A novel approach to unraveling the apoptotic potential of rutin (bioflavonoid) via targeting Jab1 in cervical cancer cells. Molecules 2021; 26(18): 5529.
[http://dx.doi.org/10.3390/molecules26185529] [PMID: 34577000]
[112]
Khan MA, Singh R, Siddiqui S, et al. Anticancer potential of Phoenix dactylifera L. seed extract in human cancer cells and proapoptotic effects mediated through caspase-3 dependent pathway in human breast cancer MDA-MB-231 cells: an in vitro and in silico investigation. BMC Complementary Medicine and Therapies 2022; 22(1): 68.
[http://dx.doi.org/10.1186/s12906-022-03533-0] [PMID: 35291987]
[113]
Boege F, Straub T, Kehr A, et al. Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I. J Biol Chem 1996; 271(4): 2262-70.
[http://dx.doi.org/10.1074/jbc.271.4.2262] [PMID: 8567688]
[114]
Chowdhury AR, Sharma S, Mandal S, Goswami A, Mukhopadhyay S, Majumder HK. Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J 2002; 366(2): 653-61.
[http://dx.doi.org/10.1042/bj20020098] [PMID: 12027807]
[115]
Cantero G, Campanella C, Mateos S, Cortés F. Topoisomerase II inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin. Mutagenesis 2006; 21(5): 321-5.
[http://dx.doi.org/10.1093/mutage/gel033] [PMID: 16950806]
[116]
Bandele OJ, Osheroff N. Bioflavonoids as poisons of human topoisomerase II α and II β. Biochemistry 2007; 46(20): 6097-108.
[http://dx.doi.org/10.1021/bi7000664] [PMID: 17458941]
[117]
López-Lázaro M, Willmore E, Austin CA. The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutat Res Genet Toxicol Environ Mutagen 2010; 696(1): 41-7.
[http://dx.doi.org/10.1016/j.mrgentox.2009.12.010] [PMID: 20025993]
[118]
Alajmi MF, Alam P, Rehman MT, et al. Interspecies anticancer and antimicrobial activities of genus solanum and estimation of rutin by validated UPLC-PDA method. Evid Based Complement Alternat Med 2018; 2018: 6040815.
[http://dx.doi.org/10.1155/2018/6040815] [PMID: 30057644]
[119]
Halliwell B, Gutteridge JM, Eds. Free radicals in biology and medicine. Oxford: Oxford University Press 2015.
[http://dx.doi.org/10.1093/acprof:oso/9780198717478.001.0001]
[120]
Slika H, Mansour H, Wehbe N, et al. Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomed Pharmacother 2022; 146: 112442.
[http://dx.doi.org/10.1016/j.biopha.2021.112442] [PMID: 35062053]
[121]
Nimse SB, Pal D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Advances 2015; 5(35): 27986-8006.
[http://dx.doi.org/10.1039/C4RA13315C]
[122]
Procházková D, Boušová I, Wilhelmová N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia 2011; 82(4): 513-23.
[http://dx.doi.org/10.1016/j.fitote.2011.01.018] [PMID: 21277359]
[123]
Lněničková K, Šadibolová M, Matoušková P, Szotáková B, Skálová L, Boušová I. The modulation of phase II drug-metabolizing enzymes in proliferating and differentiated CaCo-2 cells by Hop-derived prenylflavonoids. Nutrients 2020; 12(7): 2138.
[http://dx.doi.org/10.3390/nu12072138] [PMID: 32708388]
[124]
Cherrak SA, Mokhtari-Soulimane N, Berroukeche F, et al. In vitro antioxidant versus metal ion chelating properties of flavonoids: a structure-activity investigation. PLoS One 2016; 11(10): e0165575.
[http://dx.doi.org/10.1371/journal.pone.0165575] [PMID: 27788249]
[125]
Ferrali M, Signorini C, Caciotti B, et al. Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity. FEBS Lett 1997; 416(2): 123-9.
[http://dx.doi.org/10.1016/S0014-5793(97)01182-4] [PMID: 9369196]
[126]
Simunkova M, Barbierikova Z, Jomova K, et al. Antioxidant vs. prooxidant properties of the flavonoid, kaempferol, in the presence of Cu(II) ions: a ROS-scavenging activity, Fenton reaction and DNA damage study. Int J Mol Sci 2021; 22(4): 1619.
[http://dx.doi.org/10.3390/ijms22041619] [PMID: 33562744]
[127]
Kadoma Y, Ishihara M, Okada N, Fujisawa S. Free radical interaction between vitamin E (alpha-, beta-, gamma- and delta-tocopherol), ascorbate and flavonoids. In vivo 2006; 20(6B): 823-7.
[PMID: 17203774]
[128]
Zhu QY, Huang Y, Chen ZY. Interaction between flavonoids and α-tocopherol in human low density lipoprotein. J Nutr Biochem 2000; 11(1): 14-21.
[http://dx.doi.org/10.1016/S0955-2863(99)00065-0] [PMID: 15539338]
[129]
Zhu QY, Huang Y, Tsang D, Chen ZY. Regeneration of α-tocopherol in human low-density lipoprotein by green tea catechin. J Agric Food Chem 1999; 47(5): 2020-5.
[http://dx.doi.org/10.1021/jf9809941] [PMID: 10552489]
[130]
Amarowicza R, Pegg RB. Advances in food and nutrition research. Cambridge: Academic Press 2020; Vol. 93: pp. 251-91.
[131]
Lin S, Zhang G, Liao Y, Pan J, Gong D. Dietary flavonoids as xanthine oxidase inhibitors: structure-affinity and structure-activity relationships. J Agric Food Chem 2015; 63(35): 7784-94.
[http://dx.doi.org/10.1021/acs.jafc.5b03386] [PMID: 26285120]
[132]
Luo M, Tian R, Lu N. Quercetin inhibited endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice: critical roles for NADPH oxidase and heme oxygenase-1. J Agric Food Chem 2020; 68(39): 10875-83.
[http://dx.doi.org/10.1021/acs.jafc.0c03907] [PMID: 32880455]
[133]
Cos P, Ying L, Calomme M, et al. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 1998; 61(1): 71-6.
[http://dx.doi.org/10.1021/np970237h] [PMID: 9461655]
[134]
Huk I, Brovkovych V, Nanobash Vili J, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia–reperfusion injury: an experimental study. Br J Surg 2003; 85(8): 1080-5.
[http://dx.doi.org/10.1046/j.1365-2168.1998.00787.x] [PMID: 9718001]
[135]
Rubbo H, Radi R, Trujillo M, et al. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 1994; 269(42): 26066-75.
[http://dx.doi.org/10.1016/S0021-9258(18)47160-8] [PMID: 7929318]
[136]
Jomová K, Hudecova L, Lauro P, et al. A switch between antioxidant and prooxidant properties of the phenolic compounds myricetin, morin, 3′,4′-dihydroxyflavone, taxifolin and 4-hydroxy-coumarin in the presence of copper(II) ions: a spectroscopic, absorption titration and DNA damage study. Molecules 2019; 24(23): 4335.
[http://dx.doi.org/10.3390/molecules24234335] [PMID: 31783535]
[137]
Bayliak MM, Burdylyuk NI, Lushchak VI. Quercetin increases stress resistance in the yeast Saccharomyces cerevisiae not only as an antioxidant. Ann Microbiol 2016; 66(2): 569-76.
[http://dx.doi.org/10.1007/s13213-015-1136-8]
[138]
Lotito S, Frei B. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: Cause, consequence, or epiphenomenon? Free Radic Biol Med 2006; 41(12): 1727-46.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.04.033] [PMID: 17157175]
[139]
Shi Y, Williamson G. Quercetin lowers plasma uric acid in prehyperuricaemic males: a randomised, double-blinded, placebocontrolled, cross-over trial. Br J Nutr 2016; 115(5): 800-6.
[http://dx.doi.org/10.1017/S0007114515005310] [PMID: 26785820]
[140]
Amić D, Lučić B. Reliability of bond dissociation enthalpy calculated by the PM6 method and experimental TEAC values in antiradical QSAR of flavonoids. Bioorg Med Chem 2010; 18(1): 28-35.
[http://dx.doi.org/10.1016/j.bmc.2009.11.015] [PMID: 19944611]
[141]
Taubert D, Breitenbach T, Lazar A, et al. Reaction rate constants of superoxide scavenging by plant antioxidants. Free Radic Biol Med 2003; 35(12): 1599-607.
[http://dx.doi.org/10.1016/j.freeradbiomed.2003.09.005] [PMID: 14680683]
[142]
Bors W, Heller W, Michael M. Methods in enzymology. Amsterdam: Elsevier 1990; Vol. 186: pp. 343-55.
[143]
Sekher Pannala A, Chan TS, O’Brien PJ, Rice-Evans CA. Flavonoid B-ring chemistry and antioxidant activity: fast reaction kinetics. Biochem Biophys Res Commun 2001; 282(5): 1161-8.
[http://dx.doi.org/10.1006/bbrc.2001.4705] [PMID: 11302737]
[144]
Mishra B, Priyadarsini KI, Kumar MS, Unnikrishnan MK, Mohan H. Effect of O -glycosilation on the antioxidant activity and free radical reactions of a plant flavonoid, chrysoeriol. Bioorg Med Chem 2003; 11(13): 2677-85.
[http://dx.doi.org/10.1016/S0968-0896(03)00232-3] [PMID: 12788341]
[145]
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20(7): 933-56.
[http://dx.doi.org/10.1016/0891-5849(95)02227-9] [PMID: 8743980]
[146]
Firuzi O, Lacanna A, Petrucci R, Marrosu G, Saso L. Evaluation of the antioxidant activity of flavonoids by “ferric reducing antioxidant power” assay and cyclic voltammetry. Biochim biophys acta, gen subj 2005; 1721(1-3): 174-84.
[http://dx.doi.org/10.1016/j.bbagen.2004.11.001] [PMID: 15652192]
[147]
Dugas AJ Jr, Castañeda-Acosta J, Bonin GC, Price KL, Fischer NH, Winston GW. Evaluation of the total peroxyl radical-scavenging capacity of flavonoids: structure-activity relationships. J Nat Prod 2000; 63(3): 327-31.
[http://dx.doi.org/10.1021/np990352n] [PMID: 10757712]
[148]
Croft KD. The chemistry and biological effects of flavonoids and phenolic acids. Ann N Y Acad Sci 1998; 854(1): 435-42.
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb09922.x] [PMID: 9928450]
[149]
Bhatt AP, Redinbo MR, Bultman SJ. The role of the microbiome in cancer development and therapy. CA Cancer J Clin 2017; 67(4): 326-44.
[http://dx.doi.org/10.3322/caac.21398] [PMID: 28481406]
[150]
Wang M, Yu F, Zhang Y, Chang W, Zhou M. The effects and mechanisms of flavonoids on cancer prevention and therapy: Focus on gut microbiota. Int J Biol Sci 2022; 18(4): 1451-75.
[http://dx.doi.org/10.7150/ijbs.68170] [PMID: 35280689]
[151]
Messaoudene M, Pidgeon R, Richard C, et al. A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota. Cancer Discov 2022; 12(4): 1070-87.
[http://dx.doi.org/10.1158/2159-8290.CD-21-0808] [PMID: 35031549]
[152]
Martínez-Pérez C, Ward C, Turnbull AK, et al. Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models. Br J Cancer 2016; 114(8): 905-16.
[http://dx.doi.org/10.1038/bjc.2016.6] [PMID: 27031849]
[153]
Li J, Xiong C, Xu P, Luo Q, Zhang R. Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway. Bioengineered 2021; 12(1): 402-13.
[http://dx.doi.org/10.1080/21655979.2020.1868733] [PMID: 33356808]
[154]
Zhang Y, Zhang R, Ni H. Eriodictyol exerts potent anticancer activity against A549 human lung cancer cell line by inducing mitochondrial-mediated apoptosis, G2/M cell cycle arrest and inhibition of m-TOR/PI3K/Akt signalling pathway. Arch Med Sci 2020; 16(2): 446-52.
[http://dx.doi.org/10.5114/aoms.2019.85152] [PMID: 32190156]
[155]
Teng YN, Lin KI, Lin YC, Thang TD, Lan YH, Hung CC. A novel flavonoid from Fissistigma cupreonitens, 5 hydroxy 7,8 dimethoxyflavanone, competitively inhibited the efflux function of human Pglycoprotein and reversed cancer multi-drug resistance. Phytomedicine 2021; 85: 153528.
[http://dx.doi.org/10.1016/j.phymed.2021.153528] [PMID: 33735724]
[156]
Kocyigit A, Selek S. Exogenous antioxidants are double-edged swords. Bezmialem Sci 2016; 4(2): 70-5.
[http://dx.doi.org/10.14235/bs.2016.704]
[157]
Kejík Z, Kaplánek R, Masařík M, et al. Iron complexes of flavonoids-antioxidant capacity and beyond. Int J Mol Sci 2021; 22(2): 646.
[http://dx.doi.org/10.3390/ijms22020646] [PMID: 33440733]
[158]
Eghbaliferiz S, Iranshahi M. Prooxidant activity of polyphenols, flavonoids, anthocyanins and carotenoids: updated review of mechanisms and catalyzing metals. Phytother Res 2016; 30(9): 1379-91.
[http://dx.doi.org/10.1002/ptr.5643] [PMID: 27241122]
[159]
Wätjen W, Michels G, Steffan B, et al. Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis. J Nutr 2005; 135(3): 525-31.
[http://dx.doi.org/10.1093/jn/135.3.525] [PMID: 15735088]
[160]
Wang Y, Qi H, Liu Y, et al. The double-edged roles of ROS in cancer prevention and therapy. Theranostics 2021; 11(10): 4839-57.
[http://dx.doi.org/10.7150/thno.56747] [PMID: 33754031]
[161]
Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB. Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ 2008; 15(1): 171-82.
[http://dx.doi.org/10.1038/sj.cdd.4402233] [PMID: 17917680]
[162]
Wang K, Liu R, Li J, et al. Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling. Autophagy 2011; 7(9): 966-78.
[http://dx.doi.org/10.4161/auto.7.9.15863] [PMID: 21610320]
[163]
Li B, Lu M, Jiang XX, Pan MX, Mao JW, Chen M. Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcinoma. J Nat Med 2017; 71(2): 433-41.
[http://dx.doi.org/10.1007/s11418-017-1076-7] [PMID: 28176233]
[164]
Yang J, Pi C, Wang G. Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed Pharmacother 2018; 103: 699-707.
[http://dx.doi.org/10.1016/j.biopha.2018.04.072] [PMID: 29680738]
[165]
Bahrami A, Makiabadi E, Jalali S, Heidari Z, Assadi M, Rashidkhani B. Dietary intake of polyphenols and the risk of breast cancer: a case-control study. Clin Nutr Res 2021; 10(4): 330-40.
[http://dx.doi.org/10.7762/cnr.2021.10.4.330] [PMID: 34796137]
[166]
Londoño C, Cayssials V, de Villasante I, et al. Polyphenol intake and epithelial ovarian cancer risk in the European prospective investiga-tion into cancer and nutrition (EPIC) study. Antioxidants 2021; 10(8): 1249.
[http://dx.doi.org/10.3390/antiox10081249] [PMID: 34439497]
[167]
Bever AM, Cassidy A, Rimm EB, Stampfer MJ, Cote DJ. A prospective study of dietary flavonoid intake and risk of glioma in US men and women. Am J Clin Nutr 2021; 114(4): 1314-27.
[http://dx.doi.org/10.1093/ajcn/nqab178] [PMID: 34113960]
[168]
Hidaka A, Harrison TA, Cao Y, et al. Intake of dietary fruit, vegetables, and fiber and risk of colorectal cancer according to molecular sub-types: a pooled analysis of 9 studies. Cancer Res 2020; 80(20): 4578-90.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-0168] [PMID: 32816852]
[169]
Pereira-Wilson C. Can dietary flavonoids be useful in the personalized treatment of colorectal cancer? World J Gastrointest Oncol 2022; 14(6): 1115-23.
[http://dx.doi.org/10.4251/wjgo.v14.i6.1115] [PMID: 35949218]
[170]
Bouayed J, Bohn T. Exogenous antioxidants--Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev 2010; 3(4): 228-37.
[http://dx.doi.org/10.4161/oxim.3.4.12858] [PMID: 20972369]
[171]
Martin KR, Appel CL. Polyphenols as dietary supplements: a double-edged sword. Nutr Diet Suppl 2010; 2: 1-12.
[172]
Zhang Z, Shi J, Nice EC, Huang C, Shi Z. The multifaceted role of flavonoids in cancer therapy: leveraging autophagy with a double-edged sword. Antioxidants 2021; 10(7): 1138.
[http://dx.doi.org/10.3390/antiox10071138] [PMID: 34356371]

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