Abstract
Over the years, natural compounds have become a significant advancement in cancer treatment, primarily due to their effectiveness, safety, bio-functionality, and wide range of molecular structures. They are now increasingly preferred in drug discovery due to these attributes. These compounds, whether occurring naturally or with synthetic modifications, find applications in various fields like biology, medicine, and engineering.
While chemotherapy has been a successful method for treating cancer, it comes with systemic toxicity. To address this issue, researchers and medical practitioners are exploring the concept of combinational chemotherapy. This approach aims to reduce toxicity by using a mix of natural substances and their derivatives in clinical trials and prescription medications.
Among the most extensively studied natural anticancer compounds are quercetin, curcumin, vincristine, and vinblastine. These compounds play crucial roles as immunotherapeutics and chemosensitizers, both as standalone treatments and in combination therapies with specific mechanisms. This review article provides a concise overview of the functions, potentials, and combinations of natural anticancer compounds in cancer treatment, along with their mechanisms of action and clinical applications.
Keywords: Natural anticancer compounds, chemotherapy, immune-therapeutics, chemo-sensitizers, phytoconstituents, cancer treatment.
[http://dx.doi.org/10.1080/10408398.2021.1913091] [PMID: 33890518]
[http://dx.doi.org/10.1093/jnci/djab204] [PMID: 34743211]
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.1016/j.jcrpr.2017.07.001]
[http://dx.doi.org/10.3389/fphar.2022.950109] [PMID: 36160435]
[http://dx.doi.org/10.1016/j.drudis.2022.02.007] [PMID: 35182736]
[http://dx.doi.org/10.3390/cells11142209] [PMID: 35883653]
[http://dx.doi.org/10.1016/j.jconrel.2021.05.012] [PMID: 33991600]
[http://dx.doi.org/10.3390/ijms21031102] [PMID: 32046099]
[http://dx.doi.org/10.1016/j.biopha.2020.110009] [PMID: 32106381]
[http://dx.doi.org/10.1155/2021/3687700] [PMID: 34707776]
[http://dx.doi.org/10.15252/emmm.201607062] [PMID: 27852619]
[http://dx.doi.org/10.1007/978-1-4419-6306-2_20]
[http://dx.doi.org/10.1080/01635581.2021.1931698] [PMID: 34100309]
[http://dx.doi.org/10.1016/j.addr.2022.114445] [PMID: 35820601]
[http://dx.doi.org/10.1111/j.1752-4571.2008.00063.x] [PMID: 25567847]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2574] [PMID: 17283147]
[http://dx.doi.org/10.1016/j.apsb.2022.08.022] [PMID: 36386472]
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[http://dx.doi.org/10.1021/acs.jnatprod.9b01285] [PMID: 32162523]
[http://dx.doi.org/10.1016/j.drudis.2015.01.009] [PMID: 25617672]
[http://dx.doi.org/10.3390/v13061014] [PMID: 34071559]
[http://dx.doi.org/10.1007/s13167-021-00242-5] [PMID: 34025826]
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[http://dx.doi.org/10.1021/jm300288g] [PMID: 22537178]
[http://dx.doi.org/10.1016/B978-0-12-816455-6.00015-9]
[http://dx.doi.org/10.1016/S0040-4020(01)00271-X]
[http://dx.doi.org/10.3390/molecules27154818] [PMID: 35956766]
[http://dx.doi.org/10.1016/B978-0-12-817890-4.00006-8]
[http://dx.doi.org/10.1016/j.ejps.2009.02.018]
[http://dx.doi.org/10.1016/S0168-3659(02)00320-6] [PMID: 12490371]
[http://dx.doi.org/10.1002/ijc.11615] [PMID: 14696107]
[http://dx.doi.org/10.1016/j.colsurfb.2018.02.046] [PMID: 29604567]
[http://dx.doi.org/10.3390/ijms22063037] [PMID: 33809762]
[http://dx.doi.org/10.1016/j.jcis.2015.10.022] [PMID: 26479200]
[http://dx.doi.org/10.1016/j.ijpharm.2009.12.044]
[http://dx.doi.org/10.1016/j.jconrel.2008.01.013] [PMID: 18336946]
[http://dx.doi.org/10.1016/j.colsurfb.2015.12.048] [PMID: 26764113]
[http://dx.doi.org/10.1016/j.biopha.2014.08.013] [PMID: 25194441]
[http://dx.doi.org/10.1016/j.jcrysgro.2020.125635]
[http://dx.doi.org/10.3389/fonc.2021.660712] [PMID: 33912467]
[PMID: 26537958]
[http://dx.doi.org/10.1142/9789813208575_0002]
[http://dx.doi.org/10.2174/1381612826666200122122804] [PMID: 31969092]
[http://dx.doi.org/10.1016/B978-0-12-819937-4.00007-8]
[http://dx.doi.org/10.3390/biom10050709] [PMID: 32375296]
[http://dx.doi.org/10.1016/j.jff.2019.103553]
[http://dx.doi.org/10.1016/j.jnutbio.2018.09.022] [PMID: 30342318]
[PMID: 31579438]
[http://dx.doi.org/10.1038/s41598-019-41444-2] [PMID: 31015523]
[http://dx.doi.org/10.38212/2224-6614.1219] [PMID: 31883602]
[http://dx.doi.org/10.1016/j.cellimm.2016.11.002] [PMID: 27825563]
[http://dx.doi.org/10.1517/13543781003727057 ] [PMID: 20374035]
[http://dx.doi.org/10.4161/onci.21494] [PMID: 23170259]
[http://dx.doi.org/10.1371/journal.pone.0122374] [PMID: 25825910]
[http://dx.doi.org/10.5754/hge12046] [PMID: 22440189]
[http://dx.doi.org/10.1016/j.intimp.2013.04.017] [PMID: 23639256]
[http://dx.doi.org/10.1177/0394632017736673] [PMID: 28994628]
[http://dx.doi.org/10.1016/j.intimp.2011.01.007] [PMID: 21244860]
[http://dx.doi.org/10.1007/s11655-016-2734-4] [PMID: 27796822]
[http://dx.doi.org/10.1080/10245330310001652437] [PMID: 14965867]
[PMID: 16212923]
[http://dx.doi.org/10.1039/C9FO00865A] [PMID: 31276149]
[http://dx.doi.org/10.1016/j.bcp.2004.04.015] [PMID: 15242811]
[http://dx.doi.org/10.1016/j.biopha.2019.109570] [PMID: 31710893]
[PMID: 22490576]
[http://dx.doi.org/10.1111/j.1574-695X.2011.00845.x] [PMID: 22077226]
[http://dx.doi.org/10.3390/molecules16108343] [PMID: 21963624]
[http://dx.doi.org/10.1615/CritRevImmunol.v31.i4.10] [PMID: 21899511]
[http://dx.doi.org/10.1111/cas.13194] [PMID: 28188673]
[PMID: 27371844]
[http://dx.doi.org/10.1038/s41419-019-1638-6] [PMID: 31138779]
[http://dx.doi.org/10.1016/j.intimp.2012.06.016] [PMID: 22749847]
[http://dx.doi.org/10.1111/bph.14816] [PMID: 31368509]
[http://dx.doi.org/10.1016/j.semcancer.2016.08.006]
[http://dx.doi.org/10.1002/jcp.28253] [PMID: 30805937]
[http://dx.doi.org/10.1186/s13046-017-0661-7] [PMID: 29273065]
[http://dx.doi.org/10.1007/s11626-018-0288-9] [PMID: 30136034 ]
[http://dx.doi.org/10.1155/2019/4619865] [PMID: 30984336]
[http://dx.doi.org/10.1007/s12013-014-0438-y] [PMID: 25510462]
[http://dx.doi.org/10.1002/jcb.25937] [PMID: 28214344]
[http://dx.doi.org/10.1016/j.biopha.2017.09.062] [PMID: 28946186]
[http://dx.doi.org/10.1248/bpb.b18-00002] [PMID: 29848900]
[http://dx.doi.org/10.1142/S0192415X17500215] [PMID: 28231748]
[http://dx.doi.org/10.1186/s12935-019-0769-2] [PMID: 30899201]
[http://dx.doi.org/10.18632/oncotarget.24771] [PMID: 29719594]
[http://dx.doi.org/10.18632/oncotarget.5411] [PMID: 26447544]
[http://dx.doi.org/10.3892/or.2018.6552] [PMID: 30015938]
[http://dx.doi.org/10.21873/anticanres.13079] [PMID: 30591440]
[PMID: 22238500]
[http://dx.doi.org/10.1007/s13277-015-4526-4] [PMID: 26662956]
[PMID: 27508051]
[http://dx.doi.org/10.3390/cells8080794] [PMID: 31366086]
[http://dx.doi.org/10.1038/s41419-019-2177-x] [PMID: 31819048]
[http://dx.doi.org/10.4103/0973-1482.150407] [PMID: 27072230]
[http://dx.doi.org/10.1016/j.canlet.2014.11.026] [PMID: 25444914]
[http://dx.doi.org/10.1093/carcin/bgs302] [PMID: 23027625]
[http://dx.doi.org/10.1016/j.ejphar.2019.04.002] [PMID: 30959046]
[http://dx.doi.org/10.1186/s13046-017-0579-0] [PMID: 28797284]
[PMID: 29286229]
[http://dx.doi.org/10.1016/j.bbrc.2019.04.021] [PMID: 31056260]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1556/1326.2017.00389]
[http://dx.doi.org/10.1111/j.1440-1681.2008.04935.x] [PMID: 18430063]
[http://dx.doi.org/10.1080/21691401.2019.1699813] [PMID: 31852250]
[http://dx.doi.org/10.3892/ol.2017.6693] [PMID: 28943934]
[http://dx.doi.org/10.1016/j.lfs.2020.118000] [PMID: 32585246]
[http://dx.doi.org/10.3892/ijo.2017.3879] [PMID: 28259926]
[http://dx.doi.org/10.1016/j.bbrc.2015.02.131] [PMID: 25747710]
[http://dx.doi.org/10.1038/nrclinonc.2010.192] [PMID: 21116236]
[http://dx.doi.org/10.2174/1568009617666170330124819] [PMID: 28359240]
[http://dx.doi.org/10.3892/or.2018.6629] [PMID: 30106443]
[http://dx.doi.org/10.3390/molecules24183241] [PMID: 31492037]
[http://dx.doi.org/10.3892/mmr.2013.1650] [PMID: 23969579]
[http://dx.doi.org/10.3389/fonc.2019.01469] [PMID: 32010609]
[http://dx.doi.org/10.1371/journal.pone.0189864] [PMID: 29281678]
[http://dx.doi.org/10.1002/mc.20583] [PMID: 19777565]
[http://dx.doi.org/10.1089/jmf.2011.0145] [PMID: 22191568]
[http://dx.doi.org/10.1186/s12906-016-1046-8] [PMID: 26922065]
[http://dx.doi.org/10.1007/s10637-010-9601-5] [PMID: 21120579]
[http://dx.doi.org/10.1091/mbc.e14-04-0916] [PMID: 25213191]
[http://dx.doi.org/10.1093/abbs/gmy036] [PMID: 29701777]
[PMID: 30717556]
[http://dx.doi.org/10.1001/jama.2017.7630] [PMID: 28787497]
[http://dx.doi.org/10.1186/s12967-016-0786-z] [PMID: 26856330]
[PMID: 25596689]
[http://dx.doi.org/10.1016/j.fct.2011.04.014] [PMID: 21515332]
[http://dx.doi.org/10.3389/fphar.2017.00640] [PMID: 28955240]
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0694] [PMID: 19509257]
[http://dx.doi.org/10.1002/ptr.6347] [PMID: 30907037]
[http://dx.doi.org/10.4314/tjpr.v16i10.1]
[http://dx.doi.org/10.3892/ol.2015.3861] [PMID: 26870201]
[http://dx.doi.org/10.1016/j.phymed.2018.10.004] [PMID: 30466620]
[http://dx.doi.org/10.3390/ijms21103527] [PMID: 32429376]
[http://dx.doi.org/10.1016/j.jep.2017.03.033] [PMID: 28341244]
[http://dx.doi.org/10.3892/ijmm.2014.1718] [PMID: 24682388]
[http://dx.doi.org/10.1016/j.ncl.2016.06.014] [PMID: 27720005]
[http://dx.doi.org/10.18632/oncotarget.25175] [PMID: 29774132]
[http://dx.doi.org/10.1007/s13659-015-0056-4] [PMID: 25821199]
[http://dx.doi.org/10.3390/ijms17111928] [PMID: 27869737]
[http://dx.doi.org/10.1080/14786419.2016.1274888] [PMID: 28105861]
[http://dx.doi.org/10.3892/ijo.2017.3838] [PMID: 28101577]
[http://dx.doi.org/10.1111/1541-4337.12335] [PMID: 33350084]
[http://dx.doi.org/10.18632/oncotarget.9593] [PMID: 27232756]
[http://dx.doi.org/10.3390/nu8030156] [PMID: 26978396]
[http://dx.doi.org/10.1002/jsfa.4678] [PMID: 22012678]
[http://dx.doi.org/10.3892/mmr.2015.3266] [PMID: 25634350]
[http://dx.doi.org/10.2147/OTT.S154586] [PMID: 29670377]
[http://dx.doi.org/10.1016/j.biopha.2018.11.124] [PMID: 30551496]
[http://dx.doi.org/10.1038/sj.onc.1205972] [PMID: 12386816]
[http://dx.doi.org/10.1002/cbin.10132] [PMID: 23686743]
[http://dx.doi.org/10.1038/s41419-019-1769-9] [PMID: 31308358]
[http://dx.doi.org/10.1038/s41571-019-0227-z] [PMID: 31189965]
[http://dx.doi.org/10.3164/jcbn.15-7] [PMID: 26798196]
[http://dx.doi.org/10.1111/jop.12735] [PMID: 29777637]
[http://dx.doi.org/10.1007/978-981-15-5999-0_7]
[http://dx.doi.org/10.3390/molecules21121610] [PMID: 27886147]
[http://dx.doi.org/10.14740/wjon1191] [PMID: 31068988]
[http://dx.doi.org/10.3390/nu11071483] [PMID: 31261861]
[http://dx.doi.org/10.1038/s41391-018-0085-2] [PMID: 30651580]
[http://dx.doi.org/10.1371/journal.pone.0138710] [PMID: 26379052]
[http://dx.doi.org/10.3892/ol.2015.3619] [PMID: 26622852]
[http://dx.doi.org/10.18632/oncotarget.6625] [PMID: 26683363]
[http://dx.doi.org/10.3892/or.2017.5841] [PMID: 28731173]
[http://dx.doi.org/10.18632/oncotarget.10790] [PMID: 27462923]
[http://dx.doi.org/10.18632/oncotarget.3610] [PMID: 25915156]
[http://dx.doi.org/10.1093/carcin/bgw071] [PMID: 27335141]
[http://dx.doi.org/10.1016/j.cbi.2017.07.009] [PMID: 28709945]
[http://dx.doi.org/10.3892/mmr.2018.9564] [PMID: 30365080]
[http://dx.doi.org/10.1002/biof.1299] [PMID: 27219221]
[http://dx.doi.org/10.2174/1871520617666170725165717] [PMID: 28745237]
[http://dx.doi.org/10.1007/s13105-016-0537-x] [PMID: 27834040]
[http://dx.doi.org/10.1016/j.fct.2020.111570] [PMID: 32640345]
[http://dx.doi.org/10.2174/1871520618666180209152215] [PMID: 29424320]
[http://dx.doi.org/10.1007/s40495-014-0003-9] [PMID: 25774338]
[http://dx.doi.org/10.1093/jnci/66.6.1192] [PMID: 7017215]
[http://dx.doi.org/10.3390/ijms20092302] [PMID: 31075954]
[http://dx.doi.org/10.1016/j.canlet.2016.12.010] [PMID: 27998762]
[http://dx.doi.org/10.1111/cas.13847] [PMID: 30353606]
[http://dx.doi.org/10.1111/jcmm.15362] [PMID: 32558259]
[http://dx.doi.org/10.1080/01635581.2019.1665188] [PMID: 31544515]
[http://dx.doi.org/10.1038/cddis.2014.429] [PMID: 25321472]
[http://dx.doi.org/10.1254/fpj.153.147] [PMID: 30971653]
[http://dx.doi.org/10.1007/s11427-018-9461-5] [PMID: 30900169]
[http://dx.doi.org/10.1016/j.biopha.2017.11.082] [PMID: 29174033]
[http://dx.doi.org/10.1021/acs.jafc.6b01461] [PMID: 27115720]
[http://dx.doi.org/10.1016/j.phytochem.2014.10.032] [PMID: 25468714]
[http://dx.doi.org/10.18632/oncotarget.7524] [PMID: 26910280]
[http://dx.doi.org/10.3390/molecules21121758] [PMID: 28009843]
[http://dx.doi.org/10.1016/j.abb.2020.108314] [PMID: 32088220]
[http://dx.doi.org/10.7150/jca.21058] [PMID: 29151925]
[http://dx.doi.org/10.2147/CMAR.S222708] [PMID: 31686915]
[http://dx.doi.org/10.3390/molecules23030518] [PMID: 29495398]
[http://dx.doi.org/10.1002/mc.23007] [PMID: 31100197]
[PMID: 32521922]
[http://dx.doi.org/10.3892/ol.2018.8036] [PMID: 29552188]
[http://dx.doi.org/10.1016/B978-0-323-42863-7.00003-7]
[http://dx.doi.org/10.2147/IJN.S238256] [PMID: 32280218]
[http://dx.doi.org/10.3390/pharmaceutics10040232] [PMID: 30445705]
[http://dx.doi.org/10.1016/j.biomaterials.2020.119907] [PMID: 32120315]
[http://dx.doi.org/10.1016/j.msec.2016.03.080] [PMID: 27127036]
[http://dx.doi.org/10.1016/j.colsurfa.2020.124805]
[http://dx.doi.org/10.1016/j.jddst.2019.03.003]
[http://dx.doi.org/10.2147/IJN.S188335] [PMID: 30666110]
[http://dx.doi.org/10.1016/j.jddst.2019.03.010]
[http://dx.doi.org/10.1080/10717544.2017.1406558] [PMID: 29172759]
[http://dx.doi.org/10.2147/DDDT.S238955] [PMID: 32109990]
[http://dx.doi.org/10.1016/j.biomaterials.2016.05.027] [PMID: 27240160]
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00161] [PMID: 32437163]
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.073] [PMID: 28533175]
[http://dx.doi.org/10.1021/acsami.7b19577] [PMID: 29436217]
[http://dx.doi.org/10.3390/molecules27238367] [PMID: 36500466]