Abstract
Cancer is a rapidly rising health problem among the global population, and this burden causes a significant challenge for public health. Current chemotherapeutic agents have different limitations, including drug resistance and severe side effects, and it demands a robust approach to accessing promising anti-cancer therapeutics. The natural compounds have been extensively studied to identify improved therapeutic agents for cancer therapy. Withaferin A (WA) is a steroidal lactone found in Withania somnifera and possesses anti-inflammatory, antioxidant, anti-angiogenesis, and anticancer properties. Multiple studies have shown that WA treatment attenuated various cancer hallmarks by inducing apoptosis and reducing angiogenesis and metastasis with reduced side effects. WA is a promising agent for the treatment of various cancer, and it targets various signaling pathways. With recent updates, the current review highlights the therapeutic implications of WA and its molecular targets in different cancer.
[http://dx.doi.org/10.1007/s12094-007-0138-9] [PMID: 18158980]
[http://dx.doi.org/10.1016/j.biopha.2020.111124] [PMID: 33434782]
[http://dx.doi.org/10.1021/np030096l] [PMID: 12880330]
[PMID: 10956379]
[PMID: 6062297]
[http://dx.doi.org/10.1016/j.pnpbp.2007.09.011] [PMID: 17959291]
[http://dx.doi.org/10.1016/j.lfs.2003.07.007] [PMID: 14575818]
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0096] [PMID: 16818501]
[http://dx.doi.org/10.15430/JCP.2015.20.3.185] [PMID: 26473157]
[http://dx.doi.org/10.1371/journal.pone.0168488] [PMID: 28033383]
[http://dx.doi.org/10.7314/APJCP.2014.15.4.1711] [PMID: 24641396]
[http://dx.doi.org/10.18632/oncotarget.20170] [PMID: 29088802]
[http://dx.doi.org/10.1016/j.neo.2017.04.005] [PMID: 28494348]
[http://dx.doi.org/10.12659/MSM.916931] [PMID: 31512681]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1510] [PMID: 18794155]
[http://dx.doi.org/10.1371/journal.pone.0023354] [PMID: 21853114]
[http://dx.doi.org/10.3109/02841869609098486] [PMID: 8619948]
[http://dx.doi.org/10.3390/molecules26247696] [PMID: 34946778]
[http://dx.doi.org/10.1016/j.bcp.2012.08.027] [PMID: 22981382]
[http://dx.doi.org/10.1016/j.toxrep.2022.05.012]
[http://dx.doi.org/10.1002/ijc.25938] [PMID: 21538350]
[http://dx.doi.org/10.1016/j.jpba.2013.03.001] [PMID: 23584079]
[http://dx.doi.org/10.1002/bmc.4573] [PMID: 31062367]
[http://dx.doi.org/10.1016/j.jaim.2018.12.008]
[http://dx.doi.org/10.1002/mc.22050] [PMID: 24019090]
[http://dx.doi.org/10.1002/mc.22814] [PMID: 29603395]
[http://dx.doi.org/10.1016/j.biopha.2020.110383] [PMID: 32563149]
[http://dx.doi.org/10.1016/j.mito.2019.01.003] [PMID: 30685490]
[http://dx.doi.org/10.1002/mc.23266] [PMID: 33150660]
[http://dx.doi.org/10.1093/jnci/djw293] [PMID: 28040797]
[http://dx.doi.org/10.1074/jbc.M116.715219] [PMID: 27129776]
[http://dx.doi.org/10.1158/1940-6207.CAPR-20-0590] [PMID: 33509807]
[http://dx.doi.org/10.1002/mc.23440] [PMID: 35770722]
[http://dx.doi.org/10.1158/1940-6207.CAPR-13-0445] [PMID: 24824039]
[http://dx.doi.org/10.2174/1389201021666200129121843] [PMID: 31995002]
[http://dx.doi.org/10.1002/mc.20760] [PMID: 21432907]
[http://dx.doi.org/10.1186/1472-6882-11-84] [PMID: 21978374]
[http://dx.doi.org/10.1016/j.yexcr.2018.04.015] [PMID: 29689276]
[http://dx.doi.org/10.3390/ijms18051092] [PMID: 28534825]
[http://dx.doi.org/10.1002/mc.23104] [PMID: 31441116]
[http://dx.doi.org/10.18632/oncotarget.17107] [PMID: 28467815]
[http://dx.doi.org/10.1007/s10549-016-3795-y] [PMID: 27097807]
[http://dx.doi.org/10.1007/s10549-012-2239-6] [PMID: 22965833]
[http://dx.doi.org/10.5402/2012/707586]
[http://dx.doi.org/10.1016/j.tiv.2017.07.025]
[http://dx.doi.org/10.1016/j.canlet.2012.08.026] [PMID: 22935676]
[http://dx.doi.org/10.1093/carcin/bgq175] [PMID: 20724373]
[http://dx.doi.org/10.1093/carcin/bgz015] [PMID: 30698683]
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2081] [PMID: 24732433]
[http://dx.doi.org/10.1002/mc.22110] [PMID: 24293234]
[http://dx.doi.org/10.1074/jbc.M113.496844] [PMID: 24297176]
[PMID: 28365961]
[http://dx.doi.org/10.3892/ol.2021.12493]
[http://dx.doi.org/10.3390/cancers11071003] [PMID: 31319622]
[http://dx.doi.org/10.1038/s41598-018-34018-1] [PMID: 30356176]
[http://dx.doi.org/10.1158/1538-7445.AM2018-2040]
[http://dx.doi.org/10.3390/biom11020160] [PMID: 33530424]
[http://dx.doi.org/10.18632/oncotarget.27519] [PMID: 32362998]
[http://dx.doi.org/10.1016/j.ygyno.2011.11.044] [PMID: 22188785]
[http://dx.doi.org/10.14343/JCSCR.2016.4e1002] [PMID: 27668267]
[http://dx.doi.org/10.1371/journal.pone.0107596] [PMID: 25264898]
[http://dx.doi.org/10.1371/journal.pone.0042265] [PMID: 22860102]
[http://dx.doi.org/10.3389/fcell.2021.636498] [PMID: 33718372]
[http://dx.doi.org/10.1371/journal.pone.0236680] [PMID: 32722688]
[http://dx.doi.org/10.1186/s13048-019-0586-1] [PMID: 31767036]
[http://dx.doi.org/10.1016/j.bcp.2009.09.017] [PMID: 19769945]
[http://dx.doi.org/10.1016/j.canlet.2014.11.026] [PMID: 25444914]
[http://dx.doi.org/10.1016/j.biopha.2018.07.055] [PMID: 30119228]
[http://dx.doi.org/10.1016/j.bbrc.2018.06.162] [PMID: 29966656]
[http://dx.doi.org/10.1093/carcin/bgy109] [PMID: 30124785]
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0771] [PMID: 20053782]
[http://dx.doi.org/10.18632/oncotarget.7351] [PMID: 26883103]
[http://dx.doi.org/10.1016/j.bcp.2014.06.022] [PMID: 24995417]
[http://dx.doi.org/10.3892/ijmm.2014.1983] [PMID: 25351115]
[http://dx.doi.org/10.1111/jop.12353] [PMID: 26332363]
[http://dx.doi.org/10.1021/np100112p] [PMID: 20726569]
[http://dx.doi.org/10.3390/biom10050777] [PMID: 32429564]
[http://dx.doi.org/10.4236/jct.2015.68080]
[http://dx.doi.org/10.3390/antiox9111120] [PMID: 33202766]
[http://dx.doi.org/10.3389/fphys.2017.00634] [PMID: 28936177]
[http://dx.doi.org/10.1007/s10565-021-09584-2] [PMID: 33665778]
[http://dx.doi.org/10.1016/j.surg.2010.09.026] [PMID: 21134556]
[http://dx.doi.org/10.1016/j.amjsurg.2012.07.027] [PMID: 23231932]
[http://dx.doi.org/10.1007/s10495-011-0625-x] [PMID: 21710254]
[http://dx.doi.org/10.1002/mc.22423] [PMID: 26472150]
[http://dx.doi.org/10.1038/s41598-020-76722-x] [PMID: 33184347]
[http://dx.doi.org/10.3390/cancers11040453] [PMID: 30934990]
[http://dx.doi.org/10.4314/tjpr.v14i6.10]
[http://dx.doi.org/10.1038/s41598-017-18190-4] [PMID: 29263422]
[http://dx.doi.org/10.3389/fonc.2020.628506] [PMID: 33585254]
[http://dx.doi.org/10.1371/journal.pone.0134137] [PMID: 26230090]
[http://dx.doi.org/10.1021/np400441f] [PMID: 24079846]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2430] [PMID: 17185378]
[http://dx.doi.org/10.18632/oncotarget.10733] [PMID: 27447565]
[http://dx.doi.org/10.1002/mc.23240] [PMID: 32743846]
[http://dx.doi.org/10.1093/carcin/bgr192] [PMID: 21859835]
[http://dx.doi.org/10.3892/or.2013.2487] [PMID: 23708780]
[http://dx.doi.org/10.4110/in.2015.15.6.269] [PMID: 26770181]
[http://dx.doi.org/10.3892/ol.2017.6169] [PMID: 28693185]
[http://dx.doi.org/10.1111/cas.12988] [PMID: 27311589]
[PMID: 26884834]
[http://dx.doi.org/10.1007/s10495-008-0273-y] [PMID: 19002588]
[http://dx.doi.org/10.3390/biom12020212] [PMID: 35204712]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1125] [PMID: 17317825]
[http://dx.doi.org/10.4161/cc.6.17.4633] [PMID: 17786050]
[http://dx.doi.org/10.1007/s00018-011-0735-1] [PMID: 21637948]
[http://dx.doi.org/10.1016/j.chembiol.2007.04.010] [PMID: 17584610]
[http://dx.doi.org/10.1158/2159-8290.CD-20-0868] [PMID: 32988960]
[http://dx.doi.org/10.1517/13543780802565791] [PMID: 19053881]
[http://dx.doi.org/10.1097/00001813-200507000-00002] [PMID: 15930886]
[PMID: 31218097]
[http://dx.doi.org/10.1245/s10434-009-0655-6] [PMID: 19653042]
[http://dx.doi.org/10.1007/s12672-011-0066-6] [PMID: 21761332]
[http://dx.doi.org/10.1007/s00428-005-1264-9] [PMID: 15856292]
[http://dx.doi.org/10.1016/j.bcp.2014.08.004] [PMID: 25159986]
[http://dx.doi.org/10.1016/j.intimp.2009.02.002] [PMID: 19236958]
[http://dx.doi.org/10.1007/s10456-004-1026-3] [PMID: 15516832]