Abstract
Lung cancer is often associated with the second leading cause of mortality in males globally. Despite clinical advancements, their incidence in humans has not decreased. Hence identifying and developing alternative or complementary therapeutic agents with evidence targeting lung cancer is of considerable interest. Ursolic Acid (UA): a dietary flavonoid present in herbs, vegetables, and fruits can effectively alleviate the hallmarks of lung cancer. As a molecular therapeutic agent, UA disrupts prolonged inflammation, augments antioxidant enzyme defense, attenuates tumor growth signal and tissue invasion/metastasis, limits unrestrained proliferation, fosters apoptosis and regulates immune response in lung cancer. This review will most notably focus on the current source of UA availability, phytochemistry, bioavailability, safety, toxicity, and salient pharmacotherapeutic properties in addition to the preclinical and clinical information currently available to recommend UA as a potential therapeutic agent for lung cancer targeting and prevention.
Graphical Abstract
[http://dx.doi.org/10.1016/j.ccm.2019.10.001] [PMID: 32008623]
[http://dx.doi.org/10.21037/tlcr.2018.05.06] [PMID: 30050761]
[http://dx.doi.org/10.3414/ME0551] [PMID: 19387505]
[http://dx.doi.org/10.1016/S0140-6736(16)31340-X] [PMID: 27598680]
[http://dx.doi.org/10.1002/ijc.25516] [PMID: 21351269]
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[http://dx.doi.org/10.3390/ijerph15112608] [PMID: 30469439]
[http://dx.doi.org/10.1186/1471-2458-11-928] [PMID: 22171573]
[http://dx.doi.org/10.1158/1055-9965.EPI-10-0036] [PMID: 20447920]
[http://dx.doi.org/10.1289/ehp.1205983] [PMID: 23665813]
[http://dx.doi.org/10.5334/aogh.2419] [PMID: 30741509]
[http://dx.doi.org/10.1016/S0278-6915(03)00021-8] [PMID: 12738186]
[http://dx.doi.org/10.1016/S0278-6915(00)00164-2] [PMID: 11267712]
[http://dx.doi.org/10.1007/174_2016_93]
[http://dx.doi.org/10.18632/oncotarget.1891] [PMID: 24722523]
[http://dx.doi.org/10.1038/bjc.2015.30] [PMID: 25734397]
[http://dx.doi.org/10.1016/S1470-2045(14)71180-5] [PMID: 25846096]
[http://dx.doi.org/10.1158/1055-9965.EPI-19-0221] [PMID: 31575553]
[http://dx.doi.org/10.1111/1759-7714.13591] [PMID: 32779385]
[http://dx.doi.org/10.3389/fonc.2020.01146] [PMID: 32760673]
[http://dx.doi.org/10.1002/ijc.31937] [PMID: 30350310]
[http://dx.doi.org/10.4103/lungindia.lungindia_333_19] [PMID: 32367839]
[http://dx.doi.org/10.1016/j.biotechadv.2018.02.002] [PMID: 29408560]
[http://dx.doi.org/10.1080/13880209.2016.1214742] [PMID: 27564455]
[http://dx.doi.org/10.1016/j.foodres.2017.10.028] [PMID: 29389599]
[http://dx.doi.org/10.1016/j.bcp.2013.03.006] [PMID: 23499879]
[http://dx.doi.org/10.1517/17425255.2013.738667] [PMID: 23134084]
[http://dx.doi.org/10.1080/10408398.2010.490883] [PMID: 21955093]
[PMID: 12907607]
[http://dx.doi.org/10.1080/10408398.2016.1203755] [PMID: 27469428]
[http://dx.doi.org/10.2174/1871520619666190704163301] [PMID: 31272361]
[http://dx.doi.org/10.1021/acs.jafc.8b06954] [PMID: 30827108]
[http://dx.doi.org/10.3390/ijms151120585] [PMID: 25391044]
[http://dx.doi.org/10.1371/journal.pone.0193451] [PMID: 29558494]
[http://dx.doi.org/10.1016/B978-0-12-814466-4.00007-0]
[http://dx.doi.org/10.1021/jf063563o] [PMID: 17488026]
[http://dx.doi.org/10.1016/j.fct.2013.01.010] [PMID: 23354393]
[http://dx.doi.org/10.1021/jf300375b] [PMID: 22490120]
[http://dx.doi.org/10.1002/jsfa.4330] [PMID: 21351105]
[http://dx.doi.org/10.3390/molecules25010210] [PMID: 31947898]
[http://dx.doi.org/10.3390/ijms13055506] [PMID: 22754311]
[http://dx.doi.org/10.4196/kjpp.2018.22.3.235] [PMID: 29719446]
[http://dx.doi.org/10.1105/tpc.110.082685] [PMID: 22128119]
[http://dx.doi.org/10.1080/10408347.2017.1390425] [PMID: 29039968]
[http://dx.doi.org/10.1016/j.lfs.2016.01.017] [PMID: 26775565]
[http://dx.doi.org/10.1016/j.ejmech.2015.01.031] [PMID: 25617694]
[http://dx.doi.org/10.1016/j.ejmech.2016.07.045] [PMID: 27484517]
[http://dx.doi.org/10.3390/molecules24152751] [PMID: 31362424]
[http://dx.doi.org/10.1016/j.neulet.2004.03.011] [PMID: 15193771]
[http://dx.doi.org/10.1016/j.neulet.2014.07.005] [PMID: 25026072]
[http://dx.doi.org/10.1016/j.clinre.2014.09.007] [PMID: 25459994]
[http://dx.doi.org/10.1016/j.bbalip.2011.10.016] [PMID: 22056763]
[http://dx.doi.org/10.1152/ajpgi.00521.2005] [PMID: 16603729]
[http://dx.doi.org/10.1371/journal.pone.0039332] [PMID: 22745735]
[http://dx.doi.org/10.1371/journal.pone.0086724] [PMID: 24489777]
[http://dx.doi.org/10.1042/BJ20061123] [PMID: 17201692]
[http://dx.doi.org/10.1016/j.bbamem.2015.05.009] [PMID: 26003534]
[http://dx.doi.org/10.3390/molecules19011317] [PMID: 24451251]
[http://dx.doi.org/10.1016/j.jphotobiol.2017.01.019] [PMID: 28152388]
[http://dx.doi.org/10.1039/C5RA15039F]
[http://dx.doi.org/10.31031/APDV.2019.06.000650]
[http://dx.doi.org/10.1111/j.2042-7158.1992.tb03646.x] [PMID: 1359067]
[http://dx.doi.org/10.1016/j.toxrep.2020.04.005] [PMID: 32435599]
[http://dx.doi.org/10.1016/j.intimp.2014.09.021] [PMID: 25281393]
[PMID: 24122993]
[http://dx.doi.org/10.1158/1541-7786.MCR-06-0348] [PMID: 17855663]
[http://dx.doi.org/10.1074/jbc.M113.455188] [PMID: 24078627]
[http://dx.doi.org/10.1016/j.canlet.2016.03.042] [PMID: 27037062]
[http://dx.doi.org/10.3390/molecules24193444] [PMID: 31547522]
[http://dx.doi.org/10.21873/invivo.11485]
[http://dx.doi.org/10.3390/molecules17089104] [PMID: 22858837]
[http://dx.doi.org/10.3389/fimmu.2020.573326] [PMID: 33178201]
[http://dx.doi.org/10.1016/j.canlet.2012.01.007] [PMID: 22261329]
[http://dx.doi.org/10.1111/bph.14793] [PMID: 31322286]
[PMID: 17352226]
[http://dx.doi.org/10.1016/j.neuint.2015.01.001] [PMID: 25582659]
[http://dx.doi.org/10.1006/bbrc.1999.0966] [PMID: 10403841]
[http://dx.doi.org/10.1002/jcb.25236] [PMID: 26012840]
[http://dx.doi.org/10.1007/s12640-018-9878-2] [PMID: 29532444]
[http://dx.doi.org/10.1016/j.lfs.2004.04.027] [PMID: 15350828]
[http://dx.doi.org/10.1016/j.molimm.2020.08.010] [PMID: 32905906]
[http://dx.doi.org/10.1038/nrc.2015.17] [PMID: 26822577]
[http://dx.doi.org/10.1142/S0192415X15500834] [PMID: 26503559]
[http://dx.doi.org/10.1038/srep14570] [PMID: 26412148]
[http://dx.doi.org/10.1016/j.febslet.2014.01.040] [PMID: 24492002]
[http://dx.doi.org/10.1128/MCB.24.23.10366-10380.2004] [PMID: 15542844]
[http://dx.doi.org/10.1039/C8NR90055H] [PMID: 29595211]
[http://dx.doi.org/10.1080/13880209.2020.1794013] [PMID: 32726164]
[http://dx.doi.org/10.1126/science.1209038] [PMID: 22116877]
[http://dx.doi.org/10.1177/2472555217701685] [PMID: 28453376]
[http://dx.doi.org/10.2174/1566524016666160523143937] [PMID: 27211800]
[http://dx.doi.org/10.3389/fimmu.2020.01337] [PMID: 32733448]
[http://dx.doi.org/10.1186/s12943-020-1138-4] [PMID: 31969156]
[http://dx.doi.org/10.1002/cncr.31978] [PMID: 30748003]
[http://dx.doi.org/10.3892/ijmm.2020.4714] [PMID: 32901853]
[http://dx.doi.org/10.1038/cddis.2014.467] [PMID: 25375374]
[http://dx.doi.org/10.1016/j.cell.2017.02.004] [PMID: 28283069]
[http://dx.doi.org/10.1111/j.1742-4658.2009.07366.x] [PMID: 19843174]
[http://dx.doi.org/10.1016/j.lfs.2013.09.030] [PMID: 24121015]
[http://dx.doi.org/10.1097/CAD.0b013e328360093b] [PMID: 23511428]
[http://dx.doi.org/10.1002/path.2595] [PMID: 19644957]
[http://dx.doi.org/10.1016/j.tiv.2011.04.014] [PMID: 21539908]
[http://dx.doi.org/10.3390/molecules22122119] [PMID: 29194373]
[http://dx.doi.org/10.1016/j.phrs.2018.11.035] [PMID: 30508677]
[http://dx.doi.org/10.3390/biom10111505] [PMID: 33147723]
[http://dx.doi.org/10.1038/nrclinonc.2015.105] [PMID: 26122183]
[http://dx.doi.org/10.1002/0470856734.ch2]
[http://dx.doi.org/10.1089/jir.2018.0019] [PMID: 29889594]
[http://dx.doi.org/10.1016/j.lfs.2015.06.004] [PMID: 26135621]
[http://dx.doi.org/10.1016/j.phymed.2010.04.006] [PMID: 20579861]
[http://dx.doi.org/10.1080/14728222.2017.1371137] [PMID: 28831824]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.2741/e563]
[http://dx.doi.org/10.1021/jf103904b] [PMID: 21175131]
[http://dx.doi.org/10.1084/jem.20100035] [PMID: 20643828]
[http://dx.doi.org/10.2147/OTT.S175956] [PMID: 30568457]
[http://dx.doi.org/10.1038/nrd.2018.148] [PMID: 30310234]
[http://dx.doi.org/10.1038/nrc3818] [PMID: 25342631]
[http://dx.doi.org/10.1016/j.jconrel.2020.01.015] [PMID: 31926193]
[http://dx.doi.org/10.1038/nrc.2017.109] [PMID: 29242642]
[http://dx.doi.org/10.1152/ajprenal.00038.2010] [PMID: 21084407]
[http://dx.doi.org/10.3892/ol.2016.5468] [PMID: 28356955]
[http://dx.doi.org/10.4314/tjpr.v17i3.13]
[http://dx.doi.org/10.1016/j.cbi.2015.06.038] [PMID: 26134000]
[http://dx.doi.org/10.18632/oncotarget.3261] [PMID: 25823660]
[http://dx.doi.org/10.1038/srep05006] [PMID: 25833312]
[http://dx.doi.org/10.1155/2011/419343] [PMID: 21716649]
[http://dx.doi.org/10.1002/tox.22891] [PMID: 31855318]
[http://dx.doi.org/10.1016/j.bbrc.2004.05.183] [PMID: 15219842]
[http://dx.doi.org/10.1088/1361-6528/aa53c6] [PMID: 28091396]
[http://dx.doi.org/10.1155/2015/809714] [PMID: 25866811]
[http://dx.doi.org/10.1155/2020/8716927] [PMID: 32149143]
[http://dx.doi.org/10.3892/ol.2019.10171] [PMID: 31186681]
[http://dx.doi.org/10.1016/j.biopha.2018.09.096] [PMID: 30248543]