Abstract
Bladder cancer carries a poor prognosis and has proven resistance to chemotherapy. Pentacyclic Triterpenoid Acids (PTAs) are natural bioactive compounds that have a well-known impact on cancer research because of their cytotoxic and chemopreventive activities. This review focuses on bladder cancer which can no longer be successfully treated by DNA damaging drugs. Unlike most of the existing drugs against bladder cancer, PTAs are non-toxic to normal cells. Collecting findings from both in vitro and in vivo studies, it has been concluded that PTAs may serve as promising agents in future bladder cancer therapy. In this review, the roles of various PTAs in bladder cancer have been explored, and their mechanisms of action in the treatment of bladder cancer have been described. Specific PTAs have been shortlisted from each of the chief skeletons of pentacyclic triterpenoids, which could be effective against bladder cancer because of their mode of action. This review thereby throws light on the multi targets and mechanisms of PTAs, which are responsible for their selective anticancer effects and provides guidelines for further research and development of new natural antitumor compounds.
Keywords: Pentacyclic triterpenoid acids, bladder cancer, chemotherapy, immunotherapy, natural bioactive compounds, specific proteins, apoptosis.
Graphical Abstract
[PMID: 10918764]
[http://dx.doi.org/10.3390/cells9051213] [PMID: 32414171]
[http://dx.doi.org/10.4103/ijc.IJC_351_18] [PMID: 30950446]
[http://dx.doi.org/10.1016/j.eururo.2016.06.010] [PMID: 27370177]
[http://dx.doi.org/10.1002/1097-0142(19950101)75:1+<316:AID-CNCR2820751314>3.0.CO;2-T] [PMID: 8001003]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-3803] [PMID: 15833884]
[http://dx.doi.org/10.1186/1741-7015-11-13] [PMID: 23327481]
[http://dx.doi.org/10.1155/2012/364919] [PMID: 22400017]
[http://dx.doi.org/10.1111/IGC.0b013e3181a12e09] [PMID: 19574766]
[http://dx.doi.org/10.1002/cncr.22031] [PMID: 16773629]
[http://dx.doi.org/10.1038/sj.bjc.6603559] [PMID: 17224927]
[http://dx.doi.org/10.1111/j.1464-410X.1988.tb09152.x] [PMID: 3277688]
[http://dx.doi.org/10.21037/amj.2020.03.07]
[http://dx.doi.org/10.3233/BLC-150010] [PMID: 30561439]
[PMID: 21509275]
[http://dx.doi.org/10.1016/S0140-6736(99)02292-8] [PMID: 10470696]
[http://dx.doi.org/10.1200/JCO.1995.13.6.1384] [PMID: 7751883]
[http://dx.doi.org/10.3389/fphar.2019.01159] [PMID: 31649535]
[http://dx.doi.org/10.1038/nature22396] [PMID: 28514441]
[http://dx.doi.org/10.1016/j.biopha.2020.110393] [PMID: 32559616]
[http://dx.doi.org/10.1002/cam4.3400] [PMID: 32841548]
[http://dx.doi.org/10.1038/s41585-020-0357-1] [PMID: 32632305]
[http://dx.doi.org/10.1097/MD.0000000000009431] [PMID: 29390572]
[http://dx.doi.org/10.3322/caac.21319] [PMID: 26641959]
[http://dx.doi.org/10.3390/molecules20011610] [PMID: 25608043]
[http://dx.doi.org/10.1590/S1677-55382010000300003] [PMID: 20602819]
[http://dx.doi.org/10.2147/OTT.S212666] [PMID: 31849495]
[http://dx.doi.org/10.1016/j.lfs.2010.11.020] [PMID: 21118697]
[http://dx.doi.org/10.1002/mnfr.200700491] [PMID: 19065582]
[http://dx.doi.org/10.1155/2015/293768] [PMID: 27034686]
[http://dx.doi.org/10.1055/s-0029-1186102] [PMID: 19742422]
[http://dx.doi.org/10.1158/1541-7786.MCR-09-0493] [PMID: 20407012]
[http://dx.doi.org/10.3390/toxins2102428] [PMID: 22069560]
[http://dx.doi.org/10.18632/oncotarget.22274] [PMID: 29348843]
[http://dx.doi.org/10.1016/j.fitote.2011.12.004] [PMID: 22178684]
[http://dx.doi.org/10.18632/oncotarget.25316] [PMID: 29899865]
[http://dx.doi.org/10.1038/nrc2129] [PMID: 17446857]
[http://dx.doi.org/10.1016/j.drudis.2013.07.018] [PMID: 23954181]
[http://dx.doi.org/10.3390/molecules201119721] [PMID: 26610440]
[PMID: 23319864]
[http://dx.doi.org/10.1111/cbdd.12682] [PMID: 26535952]
[http://dx.doi.org/10.3390/molecules13123224] [PMID: 19104487]
[http://dx.doi.org/10.1039/C4RA02784A]
[PMID: 23302988]
[PMID: 31338244]
[http://dx.doi.org/10.3892/mmr.2016.5792] [PMID: 27748864]
[http://dx.doi.org/10.2174/1871520614666140223192148]
[http://dx.doi.org/10.1016/j.bmcl.2012.08.074] [PMID: 22989532]
[http://dx.doi.org/10.1016/j.cbi.2017.07.011] [PMID: 28711658]
[http://dx.doi.org/10.1371/journal.pone.0021492] [PMID: 21731766]
[PMID: 12118187]
[http://dx.doi.org/10.1016/j.molstruc.2010.06.011]
[http://dx.doi.org/10.1055/s-2008-1074523] [PMID: 18446671]
[http://dx.doi.org/10.1080/14786419.2020.1819272] [PMID: 32954865]
[http://dx.doi.org/10.1248/cpb.41.2129] [PMID: 8118906]
[http://dx.doi.org/10.1016/0031-9422(91)85129-N] [PMID: 1367781]
[http://dx.doi.org/10.1021/jf3023996] [PMID: 23003682]
[http://dx.doi.org/10.18632/oncotarget.5751] [PMID: 26513295]
[http://dx.doi.org/10.1055/s-2000-8585] [PMID: 10909277]
[http://dx.doi.org/10.1038/s41598-017-06131-0] [PMID: 28729623]
[http://dx.doi.org/10.1016/j.canlet.2014.01.016] [PMID: 24486850]
[http://dx.doi.org/10.3892/or.2014.3239] [PMID: 24912497]
[http://dx.doi.org/10.3390/molecules14062016] [PMID: 19513002]
[http://dx.doi.org/10.1248/jhs.54.654]
[http://dx.doi.org/10.1248/yakushi.125.509] [PMID: 15930819]
[http://dx.doi.org/10.1007/s10495-008-0290-x] [PMID: 19115109]
[PMID: 12855667]
[http://dx.doi.org/10.1016/j.yexcr.2010.04.027] [PMID: 20435036]
[http://dx.doi.org/10.1016/S0959-8049(01)00231-3] [PMID: 11597399]
[http://dx.doi.org/10.15586/jkcvhl.2017.64] [PMID: 28405545]
[http://dx.doi.org/10.1016/j.ejmech.2013.10.016] [PMID: 24161703]
[http://dx.doi.org/10.1186/s13568-020-01035-1] [PMID: 32488691]
[http://dx.doi.org/10.1186/1471-2407-11-154] [PMID: 21524306]
[http://dx.doi.org/10.1186/1476-4598-9-73] [PMID: 31901224]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4759] [PMID: 17440087]
[http://dx.doi.org/10.1055/s-0030-1250203] [PMID: 20669087]
[http://dx.doi.org/10.3390/ijms18030643] [PMID: 28300756]
[http://dx.doi.org/10.4161/cc.1.3.117] [PMID: 12429925]
[http://dx.doi.org/10.2147/DDDT.S84448] [PMID: 26109845]
[http://dx.doi.org/10.1093/carcin/bgi348] [PMID: 16497706]
[http://dx.doi.org/10.1101/gad.8.1.9] [PMID: 8288131]
[http://dx.doi.org/10.1007/s000180050267] [PMID: 10065149]
[http://dx.doi.org/10.4103/tme.tme_3_17]
[http://dx.doi.org/10.1016/j.bcp.2013.03.006] [PMID: 23499879]
[http://dx.doi.org/10.1007/s11655-013-1541-4] [PMID: 24374755]
[http://dx.doi.org/10.3892/mmr.2013.1364] [PMID: 23483134]
[http://dx.doi.org/10.1111/j.1365-2559.2011.03856.x] [PMID: 21707707]
[http://dx.doi.org/10.1007/s00432-007-0193-1] [PMID: 17516089]
[http://dx.doi.org/10.1007/s00109-011-0746-2] [PMID: 21465181]
[http://dx.doi.org/10.1016/j.biochi.2012.04.006] [PMID: 22521508]
[http://dx.doi.org/10.1016/j.bbrc.2012.02.093] [PMID: 22387548]
[http://dx.doi.org/10.1016/j.bmc.2009.08.046] [PMID: 19758808]
[http://dx.doi.org/10.1016/j.cellsig.2012.09.012] [PMID: 23000344]
[http://dx.doi.org/10.1074/jbc.M210284200] [PMID: 12509415]
[http://dx.doi.org/10.1182/blood-2002-08-2501] [PMID: 12560233]
[http://dx.doi.org/10.1002/ijc.27548] [PMID: 22438101]
[http://dx.doi.org/10.1016/S0304-3835(01)00718-2] [PMID: 11734332]
[http://dx.doi.org/10.1186/1471-2407-11-371] [PMID: 21864401]
[http://dx.doi.org/10.1007/s11101-019-09623-1]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2016] [PMID: 21673052]
[http://dx.doi.org/10.1016/j.ejphar.2004.12.006] [PMID: 15680252]
[http://dx.doi.org/10.1007/s11010-014-2038-y] [PMID: 24687305]
[PMID: 26823699]
[http://dx.doi.org/10.1016/j.bmcl.2008.03.031] [PMID: 18359628]
[http://dx.doi.org/10.3892/mmr.2021.12079] [PMID: 33846804]
[http://dx.doi.org/10.1371/journal.pone.0082293] [PMID: 24358166]
[http://dx.doi.org/10.1016/j.ejphar.2011.07.037] [PMID: 21839077]
[http://dx.doi.org/10.1016/j.biopha.2018.09.096] [PMID: 30248543]
[http://dx.doi.org/10.1016/j.drudis.2009.05.015] [PMID: 19520182]
[PMID: 15057642]
[http://dx.doi.org/10.1007/s13277-015-4655-9] [PMID: 26687646]
[http://dx.doi.org/10.3892/ol.2019.10171] [PMID: 31186681]
[http://dx.doi.org/10.3892/or.2015.3755] [PMID: 25633045]
[http://dx.doi.org/10.1371/journal.pone.0125709] [PMID: 25938234]
[http://dx.doi.org/10.1089/ars.2010.3221] [PMID: 20446772]
[http://dx.doi.org/10.1371/journal.pone.0005757] [PMID: 19484125]
[http://dx.doi.org/10.1111/j.1365-2125.2012.04425.x] [PMID: 22897361]