Abstract
Background: Tumor recurrence and metastasis are still leading causes of cancer mortality worldwide. The influence of traditional treatment strategies against metastatic tumors may still be limited. To search for novel and powerful agents against tumors has become a major research focus. In this study, Artemisinin (ARM), a natural compound isolated from herbs, Artemisia annua L., proceeding from drug repurposing methods, attracts more attention due to its good efficacy and tolerance in antimalarial practices, as well as newly confirmed anticancer activity.
Methods: We have searched and reviewed the literatures about ARM and its derivatives (ARMs) for cancer using keywords "artemisinin" until May 2019.
Results: In preclinical studies, ARMs can induce cell cycle arrest and cell death by apoptosis etc., to inhibit the progression of tumors, and suppress EMT and angiogenesis to inhibit the metastasis of tumors. Notably, the complex relationships of ARMs and autophagy are worth exploring. Inspired by the limitations of its antimalarial applications and the mechanical studies of artemisinin and cancer, people are also committed to develop safer and more potent ARM-based modified compounds (ARMs) or combination therapy, such as artemisinin dimers/ trimers, artemisinin-derived hybrids. Some clinical trials support artemisinins as promising candidates for cancer therapy.
Conclusion: ARMs show potent therapeutic potentials against carcinoma including metastatic tumors. Novel compounds derived from artemisinin and relevant combination therapies are supposed to be promising treatment strategies for tumors, as the important future research directions.
Keywords: Artemisinin, carcinoma, tumorigenesis, metastasis, mechanism of action, chemical modification.
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]
[http://dx.doi.org/10.1126/science.3887571] [PMID: 3887571]
[http://dx.doi.org/10.1016/S0165-6147(99)01302-4] [PMID: 10354615]
[http://dx.doi.org/10.1016/j.phrs.2016.11.012] [PMID: 27867026]
[http://dx.doi.org/10.1128/AAC.00288-18] [PMID: 29712656]
[http://dx.doi.org/10.1016/j.pharmthera.2013.12.001] [PMID: 24316259]
[http://dx.doi.org/10.1038/bjp.2008.11] [PMID: 18264129]
[http://dx.doi.org/10.1002/cam4.1276] [PMID: 29277967]
[http://dx.doi.org/10.1038/s41419-018-1006-y] [PMID: 30323180]
[http://dx.doi.org/10.1021/acs.jmedchem.5b01380] [PMID: 27010926]
[http://dx.doi.org/10.1021/np50096a007] [PMID: 8350087]
[http://dx.doi.org/10.1007/s00280-011-1643-7] [PMID: 21479633]
[http://dx.doi.org/10.1016/j.biopha.2016.04.061] [PMID: 27470341]
[http://dx.doi.org/10.1093/carcin/bgn214] [PMID: 18784357]
[http://dx.doi.org/10.1002/med.21446] [PMID: 28643446]
[http://dx.doi.org/10.1016/j.semcancer.2017.02.009] [PMID: 28254675]
[http://dx.doi.org/10.1016/j.canlet.2005.07.001] [PMID: 16111806]
[PMID: 6243376]
[http://dx.doi.org/10.1111/jcmm.13008] [PMID: 27860262]
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[http://dx.doi.org/10.1016/j.phymed.2015.08.002] [PMID: 26407947]
[http://dx.doi.org/10.1016/j.canlet.2016.07.033] [PMID: 27477901]
[http://dx.doi.org/10.1016/j.redox.2016.12.010] [PMID: 28012440]
[http://dx.doi.org/10.1002/hep.28251] [PMID: 26403645]
[PMID: 8720313]
[http://dx.doi.org/10.1111/j.1582-4934.2008.00360.x] [PMID: 18466355]
[http://dx.doi.org/10.1016/j.yexmp.2019.01.006] [PMID: 30660598]
[http://dx.doi.org/10.1016/j.sjbs.2018.04.003] [PMID: 30505200]
[http://dx.doi.org/10.1007/s10495-015-1132-2] [PMID: 25935454]
[http://dx.doi.org/10.3892/ijmm.2012.1176] [PMID: 23138847]
[http://dx.doi.org/10.1016/j.yexcr.2015.07.004] [PMID: 26163896]
[http://dx.doi.org/10.1016/j.lfs.2017.11.008] [PMID: 29128513]
[http://dx.doi.org/10.1093/abbs/gmy125] [PMID: 30395153]
[http://dx.doi.org/10.1002/mc.22582] [PMID: 27787915]
[http://dx.doi.org/10.1530/ERC-17-0261] [PMID: 29066501]
[http://dx.doi.org/10.1016/j.biopha.2013.01.013] [PMID: 23582790]
[http://dx.doi.org/10.1016/j.canlet.2013.09.035] [PMID: 24099910]
[PMID: 24518199]
[http://dx.doi.org/10.1016/j.phymed.2018.09.221] [PMID: 30599894]
[http://dx.doi.org/10.1074/jbc.M110.210047] [PMID: 21149439]
[http://dx.doi.org/10.1016/j.redox.2018.07.025] [PMID: 30196190]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[PMID: 21156967]
[http://dx.doi.org/10.1002/mc.22474] [PMID: 26878598]
[http://dx.doi.org/10.1007/s12282-018-0873-5] [PMID: 29797234]
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[http://dx.doi.org/10.18632/oncotarget.8920] [PMID: 27119499]
[http://dx.doi.org/10.1016/j.ebiom.2016.11.026] [PMID: 27939426]
[http://dx.doi.org/10.3892/or.2013.2658] [PMID: 23917613]
[http://dx.doi.org/10.1038/celldisc.2017.42] [PMID: 29387451]
[http://dx.doi.org/10.1080/21691401.2018.1433187]
[http://dx.doi.org/10.1016/j.ejphar.2008.03.041] [PMID: 18448095]
[http://dx.doi.org/10.1002/jcb.27889] [PMID: 30335897]
[http://dx.doi.org/10.1080/17460441.2019.1613370] [PMID: 31070059]
[http://dx.doi.org/10.1093/abbs/gmw082] [PMID: 27590062]
[http://dx.doi.org/10.1016/j.cbi.2017.10.011] [PMID: 29031619]
[http://dx.doi.org/10.7150/jca.25082] [PMID: 30271498]
[http://dx.doi.org/10.4161/15384047.2014.955728] [PMID: 25482945]
[http://dx.doi.org/10.1155/2013/454783] [PMID: 24223058]
[http://dx.doi.org/10.1016/j.vph.2004.11.001] [PMID: 15653096]
[http://dx.doi.org/10.3892/ijmm.2015] [PMID: 25778668]
[http://dx.doi.org/10.3892/ol.2016.5223] [PMID: 28105176]
[http://dx.doi.org/10.1002/jcb.28424] [PMID: 30746754]
[http://dx.doi.org/10.1016/j.bmcl.2013.11.032] [PMID: 24332623]
[http://dx.doi.org/10.1016/j.ejmech.2016.06.035] [PMID: 27371926]
[http://dx.doi.org/10.1016/j.leukres.2017.05.007] [PMID: 28646646]
[http://dx.doi.org/10.1016/j.ejmech.2016.08.015] [PMID: 27537924]
[http://dx.doi.org/10.1016/j.bmcl.2015.11.042] [PMID: 26615886]
[http://dx.doi.org/10.1021/acsmedchemlett.8b00381] [PMID: 30429957]
[http://dx.doi.org/10.1002/cmdc.201600594] [PMID: 27973725]
[http://dx.doi.org/10.1038/s41389-019-0122-6] [PMID: 30783079]
[http://dx.doi.org/10.1097/CAD.0b013e328364a109] [PMID: 23958790]
[http://dx.doi.org/10.1007/s11655-013-1454-2] [PMID: 23771805]
[http://dx.doi.org/10.1007/s00280-010-1355-4] [PMID: 20490800]
[http://dx.doi.org/10.1159/000484118] [PMID: 29055954]
[http://dx.doi.org/10.1007/s11010-011-0716-6] [PMID: 21234653]
[http://dx.doi.org/10.1016/j.biopha.2018.05.093] [PMID: 29864620]
[http://dx.doi.org/10.1016/j.bmc.2004.05.013] [PMID: 15210144]
[http://dx.doi.org/10.1002/ijc.24496] [PMID: 19533749]
[http://dx.doi.org/10.1016/j.bmc.2009.10.019] [PMID: 19879765]
[http://dx.doi.org/10.18632/oncotarget.6896] [PMID: 26771236]
[http://dx.doi.org/10.1021/np9605495] [PMID: 9134741]
[http://dx.doi.org/10.1016/j.bmcl.2010.08.013] [PMID: 20855209]
[http://dx.doi.org/10.1248/cpb.59.1471] [PMID: 22130368]
[http://dx.doi.org/10.1002/jsfa.7759] [PMID: 27098847]
[http://dx.doi.org/10.1038/nature03201] [PMID: 15690045]
[http://dx.doi.org/10.3390/cancers11050597] [PMID: 31035440]
[http://dx.doi.org/10.4103/0973-1296.157710] [PMID: 26109756]
[http://dx.doi.org/10.1016/j.biomaterials.2015.05.036] [PMID: 26022978]
[http://dx.doi.org/10.1016/j.biomaterials.2016.08.039] [PMID: 27614161]
[http://dx.doi.org/10.1021/acsami.7b18320] [PMID: 29378409]
[http://dx.doi.org/10.1016/j.actbio.2017.03.005] [PMID: 28274767]
[http://dx.doi.org/10.18632/oncotarget.5422] [PMID: 26426994]
[http://dx.doi.org/10.1016/j.bcp.2003.12.035] [PMID: 15081868]
[http://dx.doi.org/10.1016/j.phymed.2017.11.003] [PMID: 29174651]
[PMID: 19513562]
[http://dx.doi.org/10.1016/j.bbrc.2014.01.053] [PMID: 24462866]
[http://dx.doi.org/10.18632/oncotarget.21793] [PMID: 29262602]
[http://dx.doi.org/10.1080/15384047.2015.1071738] [PMID: 26176175]
[http://dx.doi.org/10.3892/or.14.6.1599] [PMID: 16273263]
[http://dx.doi.org/10.1097/MEG.0000000000000066] [PMID: 24987823]
[http://dx.doi.org/10.2174/18715206113136660340] [PMID: 24506460]
[http://dx.doi.org/10.1016/j.biomaterials.2014.03.049] [PMID: 24726749]
[http://dx.doi.org/10.1186/s13046-017-0531-3] [PMID: 28506239]
[PMID: 25796153]
[http://dx.doi.org/10.1007/s00228-014-1754-2] [PMID: 25248945]
[http://dx.doi.org/10.1371/journal.pone.0164838] [PMID: 27736969]
[http://dx.doi.org/10.1016/j.phymed.2010.07.003] [PMID: 20739158]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0627] [PMID: 21975929]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0629] [PMID: 21978934]
[http://dx.doi.org/10.1159/000492541] [PMID: 30099443]
[http://dx.doi.org/10.1053/ctrv.2000.0210] [PMID: 11417967]
[PMID: 27528238]
[http://dx.doi.org/10.1002/jcp.27875] [PMID: 30536376]
[http://dx.doi.org/10.1038/s41568-018-0005-8] [PMID: 29643473]
[http://dx.doi.org/10.2174/15680096113139990076] [PMID: 23369096]
[http://dx.doi.org/10.1016/j.critrevonc.2018.09.017] [PMID: 30447920]
[http://dx.doi.org/10.1038/aps.2017.10] [PMID: 28479604]
[http://dx.doi.org/10.1248/bpb.25.1555] [PMID: 12499639]
[http://dx.doi.org/10.1016/j.bcp.2009.08.013] [PMID: 19698702]
[http://dx.doi.org/10.2174/1381612825666190222155700] [PMID: 30799787]
[http://dx.doi.org/10.1111/j.1476-5381.2009.00117.x] [PMID: 19298255]
[http://dx.doi.org/10.1016/j.ejmech.2015.10.040] [PMID: 26741854]
[http://dx.doi.org/10.1016/j.phymed.2015.11.001] [PMID: 26655404]
[PMID: 22199309]
[http://dx.doi.org/10.1097/SLA.0000000000001664] [PMID: 28059970]
[http://dx.doi.org/10.1016/j.ebiom.2014.11.010] [PMID: 26137537]
[http://dx.doi.org/10.3736/jcim20080206]
[http://dx.doi.org/10.4161/cbt.27223] [PMID: 24335512]
[http://dx.doi.org/10.1016/S0091-3057(00)00309-9] [PMID: 11113482]
[http://dx.doi.org/10.1016/S0361-9230(97)00339-0] [PMID: 9443840]
[http://dx.doi.org/10.1002/ana.20620] [PMID: 16240360]
[http://dx.doi.org/10.1007/s00280-016-2960-7] [PMID: 26793976]
[http://dx.doi.org/10.1007/s10549-017-4261-1] [PMID: 28439738]
[http://dx.doi.org/10.1007/s00280-018-3533-8] [PMID: 29392450]
[http://dx.doi.org/10.1186/s13046-018-0960-7] [PMID: 30477536]
[http://dx.doi.org/10.1023/A:1006532523152] [PMID: 9514101]
[http://dx.doi.org/10.1016/j.cell.2005.02.034] [PMID: 15882617]
[http://dx.doi.org/10.1159/000489982] [PMID: 29794440]
[http://dx.doi.org/10.1111/j.1745-7254.2007.00612.x] [PMID: 17588342]