Abstract
Despite technological advancement, there is no 100% effective treatment against metastatic cancer. Increasing resistance of cancer cells towards chemotherapeutic drugs along with detrimental side effects remained a concern. Thus, the urgency in developing new anticancer agents has been raised. Anticancer peptides have been proven to display potent activity against a wide variety of cancer cells. Several mode of actions describing their cytostatic and cytotoxic effect on cancer cells have been proposed which involves cell surface binding leading to membranolysis or internalization to reach their intracellular target. Understanding the mechanism of action of these anticancer peptides is important in achieving full therapeutic success. In the present article, we discuss the anticancer action of peptides accompanied by the mechanisms underpinning their toxicity to cancer cells.
Keywords: Anticancer peptides, anticancer, antitumor, mechanism of action, cytotoxicity, drug resistance, membranolysis.
Graphical Abstract
[http://dx.doi.org/10.2174/1570163812666150602144310] [PMID: 26033233]
[http://dx.doi.org/10.1186/s12929-017-0328-x] [PMID: 28320393]
[http://dx.doi.org/10.1080/14712598.2019.1652592] [PMID: 31382850]
[PMID: 21115901]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2355] [PMID: 26921335]
[http://dx.doi.org/10.1038/cddis.2013.316] [PMID: 24052077]
[http://dx.doi.org/10.1016/j.drup.2007.08.002] [PMID: 17921043]
[http://dx.doi.org/10.18632/oncotarget.21740] [PMID: 29246030]
[http://dx.doi.org/10.1242/jcs.076745] [PMID: 21245196]
[http://dx.doi.org/10.1016/j.ceb.2009.08.008] [PMID: 19781927]
[http://dx.doi.org/10.3322/canjclin.55.3.178] [PMID: 15890640]
[http://dx.doi.org/10.1038/nrc883] [PMID: 12209154]
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[http://dx.doi.org/10.1023/A:1016119328968] [PMID: 12101391]
[http://dx.doi.org/10.1038/nrm1496] [PMID: 15520809]
[http://dx.doi.org/10.1016/j.str.2013.02.024] [PMID: 23561633]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2719] [PMID: 16638854]
[http://dx.doi.org/10.4161/cbt.8.3.7424] [PMID: 19164937]
[http://dx.doi.org/10.1016/j.ccr.2008.09.002] [PMID: 18835031]
[http://dx.doi.org/10.1096/fj.201601173R] [PMID: 28183803]
[http://dx.doi.org/10.1371/journal.pone.0211187] [PMID: 30682171]
[http://dx.doi.org/10.1016/j.peptides.2011.04.024] [PMID: 21557975]
[PMID: 1748653]
[http://dx.doi.org/10.1016/j.peptides.2008.05.012] [PMID: 18584915]
[http://dx.doi.org/10.1016/j.bpj.2009.08.063] [PMID: 20159154]
[PMID: 1551864]
[http://dx.doi.org/10.1021/acs.langmuir.7b01642] [PMID: 28605904]
[http://dx.doi.org/10.1002/cbic.201402144] [PMID: 25099014]
[http://dx.doi.org/10.1074/jbc.M111.253393] [PMID: 21576247]
[http://dx.doi.org/10.1016/j.bbagen.2018.11.003] [PMID: 30419285]
[http://dx.doi.org/10.1002/jmr.1153] [PMID: 22038811]
[http://dx.doi.org/10.1371/journal.pone.0084903] [PMID: 24386436]
[http://dx.doi.org/10.1186/1475-2867-11-6] [PMID: 21392380]
[http://dx.doi.org/10.1007/s10637-017-0438-z] [PMID: 28150073]
[http://dx.doi.org/10.1371/journal.pone.0058866] [PMID: 23554944]
[http://dx.doi.org/10.1152/ajpcell.1993.264.2.C361] [PMID: 8383429]
[http://dx.doi.org/10.1016/0041-0101(91)90128-E] [PMID: 1726031]
[PMID: 7671257]
[http://dx.doi.org/10.1016/S0014-5793(01)02728-4] [PMID: 11513873]
[PMID: 8256847]
[http://dx.doi.org/10.1177/1010428317692228] [PMID: 28347249]
[http://dx.doi.org/10.7554/eLife.37689] [PMID: 30860026]
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2015] [PMID: 24741005]
[http://dx.doi.org/10.4103/ctm.ctm_11_18]
[http://dx.doi.org/10.1200/JCO.20.3.811] [PMID: 11821465]
[http://dx.doi.org/10.1039/C6MD00376A]
[http://dx.doi.org/10.1016/j.semcancer.2017.08.012] [PMID: 28870843]
[http://dx.doi.org/10.3109/1061186X.2015.1113539] [PMID: 26596643]
[http://dx.doi.org/10.3390/antibiotics8010012] [PMID: 30704119]
[http://dx.doi.org/10.3389/fchem.2017.00086] [PMID: 29164103]
[http://dx.doi.org/10.1111/jfbc.12546] [PMID: 31353490]
[http://dx.doi.org/10.3390/biom8010004] [PMID: 29351202]
[http://dx.doi.org/10.1128/AAC.02340-16]
[http://dx.doi.org/10.1074/jbc.M112.372011] [PMID: 22854971]
[http://dx.doi.org/10.3390/ijms18020442] [PMID: 28218667]
[http://dx.doi.org/10.1101/cshperspect.a026104] [PMID: 26931810]
[http://dx.doi.org/10.1186/s12929-018-0470-0] [PMID: 30176860]
[http://dx.doi.org/10.2174/157489212798357949] [PMID: 21906014]
[http://dx.doi.org/10.1038/bjc.2013.266] [PMID: 23736031]
[http://dx.doi.org/10.1038/bjc.2013.74] [PMID: 23449360]
[http://dx.doi.org/10.1093/neuonc/now047] [PMID: 27022131]
[http://dx.doi.org/10.1186/s12943-017-0622-y] [PMID: 28264681]
[http://dx.doi.org/10.3390/cancers7020813] [PMID: 26010603]
[http://dx.doi.org/10.1016/j.bbamem.2014.12.016] [PMID: 25542783]
[http://dx.doi.org/10.1074/jbc.M114.561324] [PMID: 25829491]
[http://dx.doi.org/10.18632/oncotarget.19093] [PMID: 28969029]
[http://dx.doi.org/10.1038/nrc3105] [PMID: 21779011]
[http://dx.doi.org/10.1091/mbc.e04-10-0940] [PMID: 15800067]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2633] [PMID: 24449824]
[http://dx.doi.org/10.1038/s41419-019-1429-0] [PMID: 30792401]
[http://dx.doi.org/10.3390/cancers11020135] [PMID: 30678127]
[http://dx.doi.org/10.1182/blood-2006-02-003772] [PMID: 17420287]
[http://dx.doi.org/10.1182/blood-2010-01-262691] [PMID: 21048156]
[http://dx.doi.org/10.1074/jbc.M200592200] [PMID: 11893742]
[http://dx.doi.org/10.1007/s00232-007-9060-x] [PMID: 17763876]
[http://dx.doi.org/10.1038/sj.leu.2402572] [PMID: 12200695]
[http://dx.doi.org/10.1038/cddis.2013.174] [PMID: 23744352]
[http://dx.doi.org/10.1074/jbc.R112.343061] [PMID: 22822055]
[http://dx.doi.org/10.1038/nrn3765] [PMID: 24946761]
[http://dx.doi.org/10.1152/ajpcell.00102.2011] [PMID: 21543740]
[http://dx.doi.org/10.1200/JCO.2005.05.4569] [PMID: 16877732]
[http://dx.doi.org/10.1016/j.ctrv.2018.06.017] [PMID: 30032756]
[http://dx.doi.org/10.1002/bip.22748] [PMID: 26418522]