Abstract
Flavonoids are low molecular weight, polyphenolic phytochemicals, obtained from secondary metabolism of various plant compounds. They have a spectrum of pharmacological efficacies, including potential anticancer efficacy. Natural flavonoids are present in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids can attenuate or inhibit the initiation, promotion and progression of cancer by modulating various enzymes and receptors in diverse pathways that involve cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. Furthermore, in vitro, flavonoids have been shown to reverse multidrug resistance when used as chemo-adjuvants. Flavonoids (both natural and synthetic analogues) interact with several oncogenic targets through dependent and independent mechanisms to mediate their anticancer efficacy in different types of cancer cells.
Keywords: Flavonoids, secondary metabolism, anti-cancer therapies, multi-targeted agents, drug resistance, cancer cells.
[http://dx.doi.org/10.1093/ajcn/74.4.418] [PMID: 11566638]
[http://dx.doi.org/10.4314/tjpr.v7i3.14693]
[http://dx.doi.org/10.1016/j.jnutbio.2015.11.006] [PMID: 27142731]
[PMID: 11121513]
[http://dx.doi.org/10.1016/j.ejmech.2017.07.034] [PMID: 28793973]
[http://dx.doi.org/10.3390/cancers11010028] [PMID: 30597838]
[http://dx.doi.org/10.1186/s12885-015-1965-7] [PMID: 26675309]
[http://dx.doi.org/10.1016/j.canlet.2008.05.020] [PMID: 18571839]
[http://dx.doi.org/10.2478/v10102-009-0021-3] [PMID: 21217857]
[http://dx.doi.org/10.1016/j.ejphar.2004.07.034] [PMID: 15464042]
[http://dx.doi.org/10.2174/138955711795305335] [PMID: 21428901]
[http://dx.doi.org/10.3945/ajcn.116.144394] [PMID: 28100511]
[http://dx.doi.org/10.1016/j.orcp.2009.04.005] [PMID: 24345587]
[http://dx.doi.org/10.1016/j.foodres.2014.01.046]
[PMID: 25143728]
[http://dx.doi.org/10.2174/13816128113199990041] [PMID: 23701555]
[http://dx.doi.org/10.3945/ajcn.115.128728] [PMID: 27680990]
[http://dx.doi.org/10.1016/j.bcp.2017.03.021] [PMID: 28377278]
[http://dx.doi.org/10.3389/fphar.2018.00520] [PMID: 29875662]
[http://dx.doi.org/10.1002/mnfr.201200721] [PMID: 23471810]
[http://dx.doi.org/10.2174/187221311797264937] [PMID: 21827399]
[http://dx.doi.org/10.1017/S1368980009992990] [PMID: 20059796]
[http://dx.doi.org/10.1016/j.mehy.2005.02.015] [PMID: 15922113]
[http://dx.doi.org/10.1016/j.ejphar.2017.04.009] [PMID: 28412372]
[http://dx.doi.org/10.1016/j.jnutbio.2016.11.007] [PMID: 27951449]
[http://dx.doi.org/10.15283/ijsc.2012.5.1.39] [PMID: 24298354]
[http://dx.doi.org/10.1016/j.semcancer.2015.09.007] [PMID: 26590477]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.1096/fj.05-5128fje] [PMID: 16403733]
[http://dx.doi.org/10.1093/carcin/19.9.1583] [PMID: 9771928]
[http://dx.doi.org/10.1007/s10529-005-8457-9] [PMID: 16132860]
[http://dx.doi.org/10.1016/S0891-5849(99)00010-6] [PMID: 10401609]
[http://dx.doi.org/10.1016/S0278-6915(03)00117-0] [PMID: 12909261]
[http://dx.doi.org/10.1021/jf051333o] [PMID: 16131149]
[http://dx.doi.org/10.1016/S0003-9861(02)00668-9] [PMID: 12559991]
[PMID: 11751523]
[PMID: 12595758]
[http://dx.doi.org/10.1002/jcb.10737] [PMID: 14743383]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2014] [PMID: 15814656]
[http://dx.doi.org/10.3892/or.11.3.727] [PMID: 14767529]
[http://dx.doi.org/10.1074/jbc.M305063200] [PMID: 12826665]
[http://dx.doi.org/10.1016/S0014-4827(03)00410-5] [PMID: 14644160]
[http://dx.doi.org/10.1016/j.tox.2004.07.022] [PMID: 15588924]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4062] [PMID: 16651438]
[http://dx.doi.org/10.1016/j.taap.2004.08.004] [PMID: 15710173]
[PMID: 11299771]
[http://dx.doi.org/10.1016/S0959-8049(99)00168-9] [PMID: 10673981]
[http://dx.doi.org/10.1093/jn/133.1.226] [PMID: 12514295]
[http://dx.doi.org/10.1038/sj.onc.1206583] [PMID: 12879015]
[http://dx.doi.org/10.1248/bpb.24.1117] [PMID: 11642314]
[http://dx.doi.org/10.1023/A:1014405730585] [PMID: 12002340]
[http://dx.doi.org/10.1023/B:AGEN.0000011802.81320.e4] [PMID: 14739618]
[http://dx.doi.org/10.1023/B:BIRY.0000016355.19999.93]
[http://dx.doi.org/10.1111/j.1530-0277.2001.tb02193.x] [PMID: 11236827]
[http://dx.doi.org/10.1007/s00403-003-0402-y] [PMID: 12811578]
[http://dx.doi.org/10.1016/S0003-9861(02)00013-9] [PMID: 12054484]
[http://dx.doi.org/10.1016/S0167-4889(01)00187-2] [PMID: 11853893]
[http://dx.doi.org/10.3892/ijo.22.1.159] [PMID: 12469199]
[http://dx.doi.org/10.1016/j.bcp.2004.02.023] [PMID: 15135307]
[http://dx.doi.org/10.1002/ijc.22790] [PMID: 17471564]
[http://dx.doi.org/10.1080/01635581.2014.904912] [PMID: 24820939]
[http://dx.doi.org/10.1207/s15327914nc5001_1] [PMID: 15572291]
[http://dx.doi.org/10.1371/journal.pone.0075604] [PMID: 24069431]
[http://dx.doi.org/10.3390/nu9080911] [PMID: 28825675]
[PMID: 29375715]
[http://dx.doi.org/10.2174/1871527317666180611090006] [PMID: 29886836]
[http://dx.doi.org/10.1208/s12248-017-0134-0] [PMID: 28842850]
[PMID: 29257319]
[http://dx.doi.org/10.1186/s12885-018-4959-4] [PMID: 30367624]
[http://dx.doi.org/10.1155/2016/9612490] [PMID: 27999608]
[http://dx.doi.org/10.1016/j.foodres.2012.07.046]
[http://dx.doi.org/10.1590/S0102-695X2011005000225]
[http://dx.doi.org/10.1590/S0102-695X2008000400008]
[http://dx.doi.org/10.1016/j.biocel.2013.10.004] [PMID: 24128857]
[http://dx.doi.org/10.1080/14786419.2014.999243] [PMID: 25674928]
[http://dx.doi.org/10.1016/j.jep.2016.11.021] [PMID: 27847336]
[http://dx.doi.org/10.1080/10286020.2014.945439] [PMID: 25434469]
[http://dx.doi.org/10.3892/mco.2014.278] [PMID: 24940499]
[http://dx.doi.org/10.1097/CJI.0b013e3181d32f22] [PMID: 20386467]
[http://dx.doi.org/10.1016/0006-2952(87)90462-X] [PMID: 2446626]
[PMID: 19449452]
[http://dx.doi.org/10.1007/s12272-015-0624-5] [PMID: 26100136]
[PMID: 22773581]
[http://dx.doi.org/10.1016/j.bbrc.2014.12.027] [PMID: 25511703]
[PMID: 18038762]
[http://dx.doi.org/10.1093/jn/129.2.399] [PMID: 10024618]
[http://dx.doi.org/10.1111/j.1582-4934.2009.00695.x] [PMID: 19220577]
[http://dx.doi.org/10.1146/annurev.nutr.20.1.485] [PMID: 10940343]
[http://dx.doi.org/10.1146/annurev.nutr.21.1.381] [PMID: 11375442]
[http://dx.doi.org/10.1038/sj.embor.7400191] [PMID: 15218528]
[http://dx.doi.org/10.1016/S1471-4914(02)00002-3] [PMID: 12524205]
[http://dx.doi.org/10.1016/j.jnutbio.2006.11.004] [PMID: 17321735]
[http://dx.doi.org/10.1038/sj.onc.1209608] [PMID: 16892092]
[http://dx.doi.org/10.1172/JCI80420] [PMID: 25642709]
[http://dx.doi.org/10.1126/science.281.5381.1305] [PMID: 9721089]
[http://dx.doi.org/10.3390/ijms9030213] [PMID: 19325744]
[http://dx.doi.org/10.18632/oncotarget.15771] [PMID: 28423637]
[http://dx.doi.org/10.1016/j.biopha.2017.01.056] [PMID: 28107698]
[http://dx.doi.org/10.1007/s11010-014-2166-4] [PMID: 25060910]
[http://dx.doi.org/10.1158/1940-6207.CAPR-14-0067] [PMID: 24894198]
[http://dx.doi.org/10.1007/s13277-015-4118-3] [PMID: 26408178]
[http://dx.doi.org/10.1371/journal.pone.0142928] [PMID: 26606169]
[http://dx.doi.org/10.1038/srep21145] [PMID: 26892033]
[http://dx.doi.org/10.1016/j.cbi.2016.07.028] [PMID: 27474067]
[http://dx.doi.org/10.1016/j.pupt.2014.09.008] [PMID: 25285988]
[http://dx.doi.org/10.1007/s11010-015-2492-1] [PMID: 26112905]
[http://dx.doi.org/10.1016/j.jphotobiol.2014.03.006] [PMID: 24705371]
[http://dx.doi.org/10.1371/journal.pone.0079201] [PMID: 24265759]
[http://dx.doi.org/10.1007/s10565-013-9251-4] [PMID: 23955116]
[http://dx.doi.org/10.1056/NEJM200008033430506] [PMID: 10922424]
[http://dx.doi.org/10.1590/S0482-50042010000400008] [PMID: 21125178]
[http://dx.doi.org/10.1016/j.cell.2006.02.001] [PMID: 16497590]
[http://dx.doi.org/10.1016/j.jaci.2009.09.017] [PMID: 20061006]
[http://dx.doi.org/10.1155/2018/1264074] [PMID: 29850614]
[http://dx.doi.org/10.1016/j.biopha.2017.06.003] [PMID: 28609844]
[http://dx.doi.org/10.1016/j.bbrc.2009.02.071] [PMID: 19233127]
[http://dx.doi.org/10.1016/j.bcp.2004.10.002] [PMID: 15627476]
[http://dx.doi.org/10.4049/jimmunol.0903991] [PMID: 20483746]
[http://dx.doi.org/10.1016/j.phrs.2009.10.005] [PMID: 19892018]
[http://dx.doi.org/10.1016/j.jss.2013.05.093] [PMID: 23993202]
[PMID: 25410928]
[http://dx.doi.org/10.1021/np9904509] [PMID: 10924197]
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[http://dx.doi.org/10.1155/2017/8386065] [PMID: 29318154]
[http://dx.doi.org/10.13181/mji.v23i4.1015]
[http://dx.doi.org/10.1016/j.fitote.2011.01.018] [PMID: 21277359]
[http://dx.doi.org/10.1016/S0955-2863(02)00208-5] [PMID: 12550068]
[http://dx.doi.org/10.1021/np970237h] [PMID: 9461655]
[http://dx.doi.org/10.1016/j.etp.2010.12.009] [PMID: 21208790]
[http://dx.doi.org/10.1002/fsn3.926] [PMID: 30847157]
[http://dx.doi.org/10.4103/0974-8490.171104] [PMID: 26941539]
[http://dx.doi.org/10.1016/j.imr.2017.01.004] [PMID: 28462147]
[http://dx.doi.org/10.1080/09735070.2017.1305225]
[http://dx.doi.org/10.1016/j.gene.2014.04.043] [PMID: 24769323]
[http://dx.doi.org/10.1002/ptr.2983] [PMID: 19827031]
[http://dx.doi.org/10.1016/j.jnutbio.2004.05.002] [PMID: 15350981]
[http://dx.doi.org/10.1155/2013/137414] [PMID: 23864953]
[http://dx.doi.org/10.1080/01635581.2016.1192201] [PMID: 27366999]
[http://dx.doi.org/10.1111/j.1742-4658.2011.08235.x] [PMID: 21740521]
[http://dx.doi.org/10.1186/1479-7364-3-3-281] [PMID: 19403462]
[http://dx.doi.org/10.2174/138920111795164048] [PMID: 21118094]
[http://dx.doi.org/10.1007/s10735-011-9363-1] [PMID: 22012127]
[http://dx.doi.org/10.1007/978-1-4419-0840-7_2]
[http://dx.doi.org/10.1186/s40880-017-0217-4] [PMID: 28629389]
[PMID: 30277144]
[http://dx.doi.org/10.18433/J3RC77] [PMID: 19470292]
[http://dx.doi.org/10.1016/j.mehy.2010.12.011] [PMID: 21247706]
[http://dx.doi.org/10.1016/j.ijpharm.2004.01.032] [PMID: 15081147]
[http://dx.doi.org/10.1002/jcb.26693] [PMID: 29363820]
[http://dx.doi.org/10.1016/j.ejmech.2017.03.033] [PMID: 28411546]
[http://dx.doi.org/10.3389/fphar.2017.00498] [PMID: 28824426]
[http://dx.doi.org/10.1177/1744806918768970] [PMID: 29623757]
[http://dx.doi.org/10.1186/s12885-018-5103-1] [PMID: 30477461]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00834] [PMID: 30351934]
[http://dx.doi.org/10.1248/bpb.28.2274] [PMID: 16327165]
[http://dx.doi.org/10.1021/jm021099i] [PMID: 12747785]
[http://dx.doi.org/10.1007/s10585-018-9903-0] [PMID: 29799080]
[http://dx.doi.org/10.1155/2017/1767198] [PMID: 28698766]