Abstract
Mitochondria are key players with a multi-functional role in many vital cellular processes, such as energy metabolism, redox regulation, calcium homeostasis, Reactive Oxygen Species (ROS) as well as in cell signaling, survival and apoptosis. These functions are mainly regulated through important enzyme signaling cascades, which if altered may influence the outcome of cell viability and apoptosis. Therefore some of the key enzymes that are vital for these signaling pathways are emerging as important targets for new anticancer agent development. Mitocans are compounds aimed at targeting mitochondria in cancer cells by altering mitochondrial functions thus causing cell growth inhibition or apoptosis. This review summarizes the till present known classes of mitocans, their mechanism of action and potential therapeutic use in different forms of cancer.
Keywords: Mithocondria, cancer, mitocans, electron transport chain, hexokinase, pyruvate dehydrogenase kinase, lactate dehydrogenase, Bcl-2.
[http://dx.doi.org/10.4236/ijcm.2011.24086]
[http://dx.doi.org/10.1111/bjd.12208 ] [PMID: 23786614]
[http://dx.doi.org/10.1016/j.mito.2013.03.009 ] [PMID: 23562877]
[http://dx.doi.org/10.1038/nm.3944 ] [PMID: 26444637]
[http://dx.doi.org/10.1016/j.coi.2007.02.001 ] [PMID: 17292599]
[http://dx.doi.org/10.1038/nrc3949 ] [PMID: 26084394]
[http://dx.doi.org/10.1182/blood-2008-04-149815 ] [PMID: 18574029]
[http://dx.doi.org/10.1038/nrd2803 ] [PMID: 19478820]
[PMID: 18591999]
[http://dx.doi.org/10.1038/sj.bjp.0707288 ] [PMID: 17519949]
[http://dx.doi.org/10.1038/nchembio.1712 ] [PMID: 25517383]
[http://dx.doi.org/10.1007/s10863-006-9060-z ] [PMID: 17294131]
[http://dx.doi.org/10.1038/nrc3803 ] [PMID: 25342630]
[http://dx.doi.org/10.1371/journal.pone.0069485 ] [PMID: 23922721]
[http://dx.doi.org/10.1038/nature11452 ] [PMID: 23023132]
[http://dx.doi.org/10.1016/j.ccell.2017.05.006 ] [PMID: 28609656]
[http://dx.doi.org/10.1186/2049-3002-2-10 ] [PMID: 25057353]
[http://dx.doi.org/10.1038/cddis.2014.38 ] [PMID: 24556680]
[http://dx.doi.org/10.1038/srep00785 ] [PMID: 23139858]
[http://dx.doi.org/10.1186/1476-4598-5-14 ] [PMID: 16595004]
[http://dx.doi.org/10.1038/nature10860 ] [PMID: 22343901]
[http://dx.doi.org/10.3390/molecules24050968 ] [PMID: 30857299]
[http://dx.doi.org/10.1016/j.ccr.2013.04.018 ] [PMID: 23707781]
[http://dx.doi.org/10.18632/oncotarget.17734 ] [PMID: 28881853]
[http://dx.doi.org/10.1042/bst0280170 ] [PMID: 10816121]
[http://dx.doi.org/10.1016/S0005-2728(98)00122-4 ] [PMID: 9714750]
[http://dx.doi.org/10.1159/000103747 ] [PMID: 17595511]
[http://dx.doi.org/10.3389/fphys.2013.00076 ] [PMID: 23596421]
[http://dx.doi.org/10.1016/j.cell.2011.02.013 ] [PMID: 21376230]
[http://dx.doi.org/10.1042/BJ20081386 ] [PMID: 19061483]
[http://dx.doi.org/10.1089/ars.2012.4883 ] [PMID: 22901241]
[http://dx.doi.org/10.3390/cancers8040040 ] [PMID: 27023612]
[http://dx.doi.org/10.1085/jgp.8.6.519 ] [PMID: 19872213]
[http://dx.doi.org/10.1128/MCB.5.5.1163 ] [PMID: 2987677]
[http://dx.doi.org/10.1016/j.cell.2017.09.019 ] [PMID: 28985563]
[http://dx.doi.org/10.3389/fimmu.2016.00052 ] [PMID: 26909082]
[http://dx.doi.org/10.1177/1010428318756203 ] [PMID: 29421992]
[http://dx.doi.org/10.4161/cc.8.23.10238 ] [PMID: 19923890]
[http://dx.doi.org/10.1089/ars.2011.4243 ] [PMID: 21883043]
[http://dx.doi.org/10.1016/j.ejpb.2012.05.014 ] [PMID: 22687572]
[http://dx.doi.org/10.1038/sj.bjc.6601360 ] [PMID: 14612885]
[http://dx.doi.org/10.2174/157489206778776952 ] [PMID: 18221044]
[PMID: 11895920]
[http://dx.doi.org/10.18632/oncotarget.1563 ] [PMID: 24196563]
[http://dx.doi.org/10.1074/jbc.M108181200 ] [PMID: 11557773]
[http://dx.doi.org/10.1084/jem.20101470 ] [PMID: 21242296]
[http://dx.doi.org/10.18632/oncotarget.13763 ] [PMID: 27926482]
[PMID: 7263678]
[http://dx.doi.org/10.1016/j.semcancer.2008.11.006 ] [PMID: 19101634]
[http://dx.doi.org/10.1074/jbc.M109950200 ] [PMID: 11751859]
[http://dx.doi.org/10.1152/ajpendo.00392.2009 ] [PMID: 19887597]
[http://dx.doi.org/10.1152/ajpendo.00417.2013 ] [PMID: 24644243]
[http://dx.doi.org/10.1016/S1440-2440(04)80273-1 ] [PMID: 15214597]
[http://dx.doi.org/10.1007/s00125-017-4342-z ] [PMID: 28776086]
[http://dx.doi.org/10.1042/BJ20140620 ] [PMID: 25017630]
[http://dx.doi.org/10.4161/cc.26461 ] [PMID: 24240433]
[PMID: 25053988]
[http://dx.doi.org/10.1042/BSR20150267 ] [PMID: 26740252]
[http://dx.doi.org/10.1016/j.ccr.2013.06.014 ] [PMID: 23911236]
[http://dx.doi.org/10.1073/pnas.1003428107 ] [PMID: 20421486]
[http://dx.doi.org/10.1186/s12935-016-0280-y ] [PMID: 26884725]
[http://dx.doi.org/10.1186/s13046-017-0530-4 ] [PMID: 28427443]
[http://dx.doi.org/10.1016/j.ccr.2006.10.020 ] [PMID: 17222789]
[http://dx.doi.org/10.18632/oncotarget.2721 ] [PMID: 25544754]
[http://dx.doi.org/10.1093/carcin/bgq012 ] [PMID: 20080835]
[http://dx.doi.org/10.1002/ijc.25499 ] [PMID: 20533281]
[http://dx.doi.org/10.1038/sj.bjc.6605701 ] [PMID: 20485289]
[http://dx.doi.org/10.1126/scitranslmed.3000677] [PMID: 20463368]
[http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e14637 ]
[http://dx.doi.org/10.3892/ijo.2015.2953 ] [PMID: 25846762]
[http://dx.doi.org/10.1002/iub.1216 ] [PMID: 24265197]
[PMID: 13654335]
[http://dx.doi.org/10.1073/pnas.0502267102 ] [PMID: 15840712]
[http://dx.doi.org/10.1016/j.canlet.2014.11.046 ] [PMID: 25524555]
[http://dx.doi.org/10.3892/or.2013.2735 ] [PMID: 24064966]
[http://dx.doi.org/10.18632/oncotarget.2620 ] [PMID: 25361010]
[http://dx.doi.org/10.3892/or.2014.3600 ] [PMID: 25394466]
[http://dx.doi.org/10.1016/j.tem.2012.06.005 ] [PMID: 22819213]
[http://dx.doi.org/10.1016/S0014-5793(01)02198-6 ] [PMID: 11248227]
[http://dx.doi.org/10.1083/jcb.200609074 ] [PMID: 17562787]
[http://dx.doi.org/10.1016/j.celrep.2014.02.046 ] [PMID: 24685140]
[http://dx.doi.org/10.1091/mbc.11.11.3977 ] [PMID: 11071921]
[http://dx.doi.org/10.1186/1741-7007-12-34 ] [PMID: 24884669]
[http://dx.doi.org/10.7554/eLife.02242 ] [PMID: 24843020]
[PMID: 18695925]
[http://dx.doi.org/10.1126/science.283.5407.1482 ] [PMID: 10066162]
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0080 ] [PMID: 23687346]
[http://dx.doi.org/10.1083/jcb.200704059 ] [PMID: 18086914]
[http://dx.doi.org/10.1038/onc.2011.167 ] [PMID: 21625217]
[http://dx.doi.org/10.1016/j.ceb.2004.09.008 ] [PMID: 15530775]
[http://dx.doi.org/10.1007/s00204-015-1520-y ] [PMID: 26047665]
[http://dx.doi.org/10.3109/10715761003667554 ] [PMID: 20370557]
[http://dx.doi.org/10.1016/0014-5793(94)80380-3 ] [PMID: 8313978]
[http://dx.doi.org/10.1074/jbc.M210432200 ] [PMID: 12496265]
[http://dx.doi.org/10.1074/jbc.M301546200 ] [PMID: 12853461]
[http://dx.doi.org/10.1083/jcb.201009132 ] [PMID: 21383081]
[http://dx.doi.org/10.1155/2013/243876 ] [PMID: 23690779]
[http://dx.doi.org/10.1023/B:APPT.0000031449.57551.e1 ] [PMID: 15192326]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4447 ] [PMID: 17638885]
[http://dx.doi.org/10.3389/fphar.2018.01073 ] [PMID: 30337872]
[http://dx.doi.org/10.1016/j.isci.2018.04.013] [PMID: 30428319]
[http://dx.doi.org/10.1016/S0304-3835(97)04716-2 ] [PMID: 9097981]
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.09.021 ] [PMID: 26453927]
[http://dx.doi.org/10.1179/1351000213Y.0000000064 ] [PMID: 24225203]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2439]
[http://dx.doi.org/10.1074/jbc.M110.186643 ] [PMID: 21059645]
[http://dx.doi.org/10.5772/intechopen.71638]
[http://dx.doi.org/10.1074/jbc.M115.697516 ] [PMID: 26521302]
[http://dx.doi.org/10.1242/jcs.011163 ] [PMID: 18032788]
[PMID: 25520856]
[http://dx.doi.org/10.18632/oncotarget.9122 ] [PMID: 27136895]
[http://dx.doi.org/10.1074/jbc.M802529200 ] [PMID: 18768478]
[http://dx.doi.org/10.1074/jbc.M611777200 ] [PMID: 17213201]
[http://dx.doi.org/10.1038/srep14296 ] [PMID: 26469226]
[http://dx.doi.org/10.1007/s00018-009-0212-2 ] [PMID: 19941060]
[http://dx.doi.org/10.1021/pr700742h ] [PMID: 18275135]
[http://dx.doi.org/10.1016/S1074-5521(00)00057-0 ] [PMID: 11182320]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4162 ] [PMID: 16651444]
[http://dx.doi.org/10.18632/oncotarget.6405 ] [PMID: 26621844]
[http://dx.doi.org/10.1074/jbc.275.10.7087 ] [PMID: 10702275]
[http://dx.doi.org/10.1074/jbc.M203080200 ] [PMID: 12431997]
[http://dx.doi.org/10.18632/oncotarget.2320 ] [PMID: 25115399]
[http://dx.doi.org/10.1038/nrm2308 ] [PMID: 18097445]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0144 ] [PMID: 19228717]
[PMID: 15542773]
[http://dx.doi.org/10.1016/j.molcel.2005.02.003 ] [PMID: 15721256]
[http://dx.doi.org/10.1016/S1535-6108(02)00127-7 ] [PMID: 12242151]
[http://dx.doi.org/10.1126/science.1102974 ] [PMID: 15353788]
[http://dx.doi.org/10.1038/35055095 ] [PMID: 11175751]
[http://dx.doi.org/10.1074/jbc.M400295200 ] [PMID: 14966123]
[http://dx.doi.org/10.1074/jbc.M513708200 ] [PMID: 16481323]
[http://dx.doi.org/10.1182/blood.V99.9.3461 ] [PMID: 11964319]
[http://dx.doi.org/10.1038/sj.leu.2403109 ] [PMID: 14513055]
[http://dx.doi.org/10.1074/jbc.M402290200 ] [PMID: 15175350]
[http://dx.doi.org/10.1038/sj.onc.1209830 ] [PMID: 16909121]
[http://dx.doi.org/10.1016/j.leukres.2006.11.010 ] [PMID: 17224180]
[http://dx.doi.org/10.1038/35055085 ] [PMID: 11175750]
[http://dx.doi.org/10.1046/j.1365-2141.2003.04268.x ] [PMID: 12694257]
[http://dx.doi.org/10.1007/s10495-005-2490-y ] [PMID: 16215673]
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3648 ] [PMID: 15150119]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0945 ] [PMID: 15520201]
[http://dx.doi.org/10.1182/blood-2007-12-129833 ] [PMID: 18292288]
[http://dx.doi.org/10.1593/neo.05691 ] [PMID: 16611409]
[http://dx.doi.org/10.1002/ijc.22910 ] [PMID: 17597109]
[http://dx.doi.org/10.1021/jm030190z ] [PMID: 13678404]
[http://dx.doi.org/10.1038/nrd2658 ] [PMID: 19043450]
[PMID: 15713891]
[http://dx.doi.org/10.1097/01.mpa.0000179731.46210.01 ] [PMID: 16258364]
[http://dx.doi.org/10.1111/j.1440-1681.2007.04577.x ] [PMID: 17250644]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-0551 ] [PMID: 15570010]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2985 ] [PMID: 19366825]
[http://dx.doi.org/10.1023/A:1010686204736 ] [PMID: 11510695]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1748 ] [PMID: 17145881]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1574 ] [PMID: 17404107]
[http://dx.doi.org/10.1152/physrev.00001.2015 ] [PMID: 26269524]
[http://dx.doi.org/10.1038/sj.onc.1207205 ] [PMID: 14647451]
[http://dx.doi.org/10.1006/excr.1999.4519 ] [PMID: 10366441]
[http://dx.doi.org/10.1038/sj.onc.1203299 ] [PMID: 10645010]
[http://dx.doi.org/10.1083/jcb.200105057 ] [PMID: 11739410]
[http://dx.doi.org/10.1042/bj20011672 ] [PMID: 12149099]
[http://dx.doi.org/10.1016/S1535-6108(03)00109-0 ] [PMID: 12781367]
[http://dx.doi.org/10.1074/jbc.273.51.33942 ] [PMID: 9852046]
[http://dx.doi.org/10.1016/S0304-3835(01)00718-2 ] [PMID: 11734332]
[http://dx.doi.org/10.1080/14786419.2010.545352 ] [PMID: 21598174]
[http://dx.doi.org/10.3390/ijms15058235 ] [PMID: 24821543]
[http://dx.doi.org/10.1007/s10330-010-0002-1]
[http://dx.doi.org/10.2174/1871520614666140223192148 ] [PMID: 24568161]
[http://dx.doi.org/10.1002/med.10053 ] [PMID: 14595673]
[http://dx.doi.org/10.1097/CAD.0b013e3283357c62 ] [PMID: 20075711]
[http://dx.doi.org/10.1177/1934578X1200700304 ] [PMID: 22545397]
[http://dx.doi.org/10.1196/annals.1427.015 ] [PMID: 19076429]
[http://dx.doi.org/10.2298/VSP1307675S ] [PMID: 23984617]
[http://dx.doi.org/10.3390/cancers2021288 ] [PMID: 24281116]
[http://dx.doi.org/10.4161/cbt.7.12.7067 ] [PMID: 18981733]
[http://dx.doi.org/10.3390/cancers3011285 ] [PMID: 24212662]
[http://dx.doi.org/10.1038/nrc706 ] [PMID: 11902585]
[http://dx.doi.org/10.1038/cddis.2013.190 ] [PMID: 23744358]
[http://dx.doi.org/10.1073/pnas.0701549104 ] [PMID: 17640917]
[http://dx.doi.org/10.1007/s12029-014-9617-8 ] [PMID: 24825822]
[http://dx.doi.org/10.1089/ars.2011.4170 ] [PMID: 21827296]
[http://dx.doi.org/10.1038/290457a0 ] [PMID: 7219534]
[http://dx.doi.org/10.1016/S0074-7742(02)53002-6 ] [PMID: 12512335]
[PMID: 20301403]
[http://dx.doi.org/10.1016/S0531-5565(01)00153-X ] [PMID: 11738157]
[PMID: 11861366]
[http://dx.doi.org/10.1385/1-59259-284-8:107 ] [PMID: 12013789]
[http://dx.doi.org/10.1038/3108 ] [PMID: 9806551]
[http://dx.doi.org/10.3748/wjg.v11.i21.3304 ] [PMID: 15929189]
[http://dx.doi.org/10.1073/pnas.1211502109 ] [PMID: 22891333]
[http://dx.doi.org/10.1080/15376520490257563 ] [PMID: 20021129]
[PMID: 8913349]
[http://dx.doi.org/10.2174/1568011054222364 ] [PMID: 16101488]
[http://dx.doi.org/10.1038/cddis.2015.305 ] [PMID: 26539916]
[http://dx.doi.org/10.1074/jbc.C000518200 ] [PMID: 10961984]
[PMID: 2842043]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1037 ] [PMID: 17020989]
[http://dx.doi.org/10.1073/pnas.1405244111 ] [PMID: 25002500]
[http://dx.doi.org/10.1016/j.chembiol.2013.08.010 ] [PMID: 24183971]
[http://dx.doi.org/10.1111/j.1349-7006.2008.00771.x ] [PMID: 18312466]
[http://dx.doi.org/10.1007/s00280-009-1016-7 ] [PMID: 19449007]
[http://dx.doi.org/10.1016/j.ddstr.2014.04.002 ] [PMID: 25558270]