Abstract
In spite of therapeutic modalities such as surgical resection, chemotherapy, and radiotherapy, Glioblastoma Multiforme (GBM) remains an incurable fatal disease. This necessitates further therapeutic options that could enhance the efficacy of existing modalities. Nitric Oxide (NO), a short-lived small molecule, has been revealed to play a crucial role in the pathophysiology of GBM. Several studies have demonstrated that NO is involved in apoptosis, metastasis, cellular proliferation, angiogenesis, invasion, and many other processes implicated in GBM pathobiology. Herein, we elaborate on the role of NO as a therapeutic target in GBM and discuss some natural products affecting the NO signaling pathway.
Keywords: Glioblastoma multiforme, nitric oxide, apoptosis, metastasis, angiogenesis, natural products.
[http://dx.doi.org/10.17179/excli2019-1136] [PMID: 31611741]
[http://dx.doi.org/10.1055/a-0986-6543] [PMID: 31499542]
[PMID: 31309072]
[http://dx.doi.org/10.1016/j.gendis.2016.04.007] [PMID: 30258889]
[http://dx.doi.org/10.1056/NEJMoa1407279] [PMID: 26061753]
[http://dx.doi.org/10.1016/j.ajpath.2015.02.023] [PMID: 25976245]
[http://dx.doi.org/10.1038/sigtrans.2017.40] [PMID: 29263927]
[PMID: 26535188]
[http://dx.doi.org/10.15430/JCP.2016.21.1.1] [PMID: 27051643]
[http://dx.doi.org/10.1016/j.niox.2016.08.002] [PMID: 27553128]
[http://dx.doi.org/10.1016/S0165-5728(01)00391-5] [PMID: 11585620]
[http://dx.doi.org/10.3390/proceedings2019022052]
[http://dx.doi.org/10.1089/ars.2016.6820] [PMID: 27411305]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1826] [PMID: 18559623]
[http://dx.doi.org/10.1006/viro.1996.0484] [PMID: 8806568]
[PMID: 14672505]
[PMID: 16724682]
[http://dx.doi.org/10.1080/02688690120057628] [PMID: 11478055]
[http://dx.doi.org/10.1007/s00401-004-0860-0] [PMID: 15088099]
[http://dx.doi.org/10.1177/1010428317703922] [PMID: 28653883]
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.02.010] [PMID: 15110396]
[http://dx.doi.org/10.1007/s13277-012-0416-1] [PMID: 22739939]
[http://dx.doi.org/10.1007/s12035-019-1513-6] [PMID: 30715649]
[PMID: 9242464]
[http://dx.doi.org/10.1016/S0002-9440(10)65240-6] [PMID: 10514420]
[http://dx.doi.org/10.1016/S0026-2862(02)00011-0] [PMID: 12535865]
[PMID: 9041200]
[http://dx.doi.org/10.1002/1097-0215(200002)9999:9999<:AID-IJC1109>3.0.CO;2-D] [PMID: 11267968]
[PMID: 11306506]
[http://dx.doi.org/10.1254/jphs.91.15] [PMID: 12686726]
[http://dx.doi.org/10.1093/neuonc/nos337] [PMID: 23328810]
[http://dx.doi.org/10.1016/j.ijrobp.2005.11.017] [PMID: 16488554]
[http://dx.doi.org/10.7150/ijms.31579] [PMID: 31171914]
[http://dx.doi.org/10.1038/sj.onc.1202154] [PMID: 9811463]
[http://dx.doi.org/10.1016/j.neuint.2006.07.001] [PMID: 16971023]
[http://dx.doi.org/10.1038/35014028] [PMID: 10854324]
[http://dx.doi.org/10.1016/j.cell.2011.06.006] [PMID: 21729780]
[http://dx.doi.org/10.1016/B978-0-12-816545-4.00005-0]
[http://dx.doi.org/10.1111/j.1439-0272.2009.00964.x] [PMID: 20384801]
[http://dx.doi.org/10.1016/j.plaphy.2010.01.007] [PMID: 20303775]
[http://dx.doi.org/10.1016/j.neures.2004.10.006] [PMID: 15681035]
[http://dx.doi.org/10.1038/416560a] [PMID: 11932750]
[http://dx.doi.org/10.1016/j.fct.2013.07.012] [PMID: 23871826]
[http://dx.doi.org/10.1073/pnas.222679399] [PMID: 12481036]
[http://dx.doi.org/10.3892/ijmm.17.6.1069] [PMID: 16685418]
[http://dx.doi.org/10.1016/j.neuro.2007.03.008] [PMID: 17498806]
[http://dx.doi.org/10.1016/j.tox.2006.03.007] [PMID: 16647178]
[http://dx.doi.org/10.3892/ijo.29.4.981] [PMID: 16964394]
[http://dx.doi.org/10.1002/glia.23234] [PMID: 28948650]
[http://dx.doi.org/10.1002/jcb.25192] [PMID: 25919965]
[http://dx.doi.org/10.1371/journal.pone.0120435] [PMID: 25768009]
[http://dx.doi.org/10.1016/j.burns.2014.05.022] [PMID: 24957357]
[http://dx.doi.org/10.1016/S1470-2045(07)70001-3] [PMID: 17267325]
[http://dx.doi.org/10.1182/blood.V95.1.189] [PMID: 10607702]
[http://dx.doi.org/10.1016/j.bone.2015.02.008] [PMID: 26453501]
[http://dx.doi.org/10.1016/j.jsbmb.2014.04.007] [PMID: 24787660]
[http://dx.doi.org/10.18632/oncotarget.11372] [PMID: 27556184]
[http://dx.doi.org/10.1016/j.ejcb.2011.03.005] [PMID: 21616556]
[http://dx.doi.org/10.21873/cgp.20021] [PMID: 28031240]
[http://dx.doi.org/10.1016/S0024-3205(00)00902-4] [PMID: 11191629]
[http://dx.doi.org/10.1038/nn.4185] [PMID: 26713745]
[http://dx.doi.org/10.1080/2162402X.2015.1056442] [PMID: 26942063]
[http://dx.doi.org/10.1038/s41598-017-14079-4] [PMID: 29062041]
[http://dx.doi.org/10.1371/journal.pone.0116644] [PMID: 25658639]
[http://dx.doi.org/10.1007/s13402-017-0337-5] [PMID: 28643230]
[http://dx.doi.org/10.1097/CEJ.0b013e32832c389e] [PMID: 19531956]
[http://dx.doi.org/10.1016/j.cytogfr.2016.10.001] [PMID: 27743775]
[http://dx.doi.org/10.1016/j.phrs.2016.12.037] [PMID: 28042086]
[http://dx.doi.org/10.1055/s-0043-100019] [PMID: 28158893]
[http://dx.doi.org/10.1080/10408398.2017.1358139] [PMID: 28799796]
[http://dx.doi.org/10.1186/s13046-018-0792-5] [PMID: 30041669]
[http://dx.doi.org/10.1016/j.ijrobp.2019.06.2287] [PMID: 30995926]
[http://dx.doi.org/10.1111/j.2042-7158.2012.01510.x] [PMID: 22943180]
[http://dx.doi.org/10.1016/S1567-5769(02)00093-0] [PMID: 12433056]
[http://dx.doi.org/10.1002/ptr.6426] [PMID: 31359523]
[http://dx.doi.org/10.1021/acs.jnatprod.8b00229] [PMID: 29799195]
[http://dx.doi.org/10.1007/s10495-015-1152-y] [PMID: 26184498]
[http://dx.doi.org/10.1016/S0367-326X(03)00062-5] [PMID: 12781805]
[http://dx.doi.org/10.1016/j.apjtb.2016.02.002]
[http://dx.doi.org/10.1016/S0024-3205(01)01425-4] [PMID: 11811897]
[http://dx.doi.org/10.1016/j.sjbs.2014.04.003] [PMID: 25313277]
[http://dx.doi.org/10.1016/j.intimp.2005.02.020] [PMID: 15914327]
[http://dx.doi.org/10.1016/j.jep.2004.06.019] [PMID: 15507334]
[http://dx.doi.org/10.1021/jf030407y] [PMID: 14664511]
[http://dx.doi.org/10.1016/S0009-8981(01)00808-7] [PMID: 11880120]
[http://dx.doi.org/10.1016/S0378-8741(02)00188-5] [PMID: 12241998]
[http://dx.doi.org/10.1016/j.jep.2004.02.028] [PMID: 15182898]
[http://dx.doi.org/10.1021/jf0259415] [PMID: 12590506]
[http://dx.doi.org/10.1016/j.jep.2005.06.028] [PMID: 16054790]
[http://dx.doi.org/10.1002/ptr.1251] [PMID: 13680825]
[http://dx.doi.org/10.1248/bpb.25.1142] [PMID: 12230105]
[http://dx.doi.org/10.1016/j.jep.2004.05.015] [PMID: 15261979]
[http://dx.doi.org/10.1016/S1567-5769(02)00212-6] [PMID: 12538034]
[http://dx.doi.org/10.1016/j.jep.2004.08.010] [PMID: 15507368]
[http://dx.doi.org/10.1016/S0378-8741(03)00228-9] [PMID: 12963157]
[http://dx.doi.org/10.1016/j.jep.2004.03.007] [PMID: 15138010]
[http://dx.doi.org/10.1016/j.jep.2005.01.059] [PMID: 15848017]
[http://dx.doi.org/10.1016/j.jep.2003.09.006] [PMID: 14698502]
[http://dx.doi.org/10.1016/j.fitote.2003.11.003] [PMID: 15030918]
[http://dx.doi.org/10.1016/j.jep.2003.11.011] [PMID: 15036463]
[http://dx.doi.org/10.1016/j.phymed.2003.12.012] [PMID: 16121519]
[http://dx.doi.org/10.1055/s-2003-40641] [PMID: 12865966]
[http://dx.doi.org/10.1021/jf049436e] [PMID: 15291469]
[http://dx.doi.org/10.1016/S0378-8741(98)00063-4] [PMID: 9741885]
[http://dx.doi.org/10.1002/ptr.1180] [PMID: 12748984]
[http://dx.doi.org/10.1006/cimm.2001.1793] [PMID: 11485347]
[http://dx.doi.org/10.1055/s-2003-42790] [PMID: 14531017]
[http://dx.doi.org/10.1016/j.jnutbio.2003.07.002] [PMID: 14559111]
[http://dx.doi.org/10.1007/BF02975885] [PMID: 15646795]
[PMID: 11037971]
[http://dx.doi.org/10.3390/10101279] [PMID: 18007520]
[http://dx.doi.org/10.1016/S0006-2952(99)00255-5] [PMID: 10535759]
[http://dx.doi.org/10.1016/j.jep.2004.06.024] [PMID: 15374609]
[http://dx.doi.org/10.1016/S0378-8741(02)00205-2] [PMID: 12413723]
[PMID: 21931202]
[http://dx.doi.org/10.1038/srep21144] [PMID: 26888313]
[http://dx.doi.org/10.1016/j.jnutbio.2009.03.013] [PMID: 19576750]
[http://dx.doi.org/10.1021/tx060157q] [PMID: 17112238]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1528] [PMID: 17200374]
[http://dx.doi.org/10.1016/j.ejphar.2014.05.031] [PMID: 24877688]
[http://dx.doi.org/10.1016/j.jep.2010.03.037] [PMID: 20371283]
[http://dx.doi.org/10.1097/00005344-199802000-00016] [PMID: 9475272]
[http://dx.doi.org/10.1016/j.lfs.2003.06.022] [PMID: 14572883]
[http://dx.doi.org/10.1055/s-2005-871287] [PMID: 16142640]
[http://dx.doi.org/10.1248/bpb.26.61] [PMID: 12520174]
[http://dx.doi.org/10.1248/cpb.52.1326] [PMID: 15516755]
[http://dx.doi.org/10.1016/S0006-2952(99)00160-4] [PMID: 10449184]
[http://dx.doi.org/10.1016/S0006-2952(01)00594-9] [PMID: 11331078]
[http://dx.doi.org/10.4049/jimmunol.179.10.7121] [PMID: 17982104]
[http://dx.doi.org/10.1002/mnfr.200500103] [PMID: 16254887]
[http://dx.doi.org/10.1021/jf001198+] [PMID: 11308324]
[http://dx.doi.org/10.3181/0810-RM-298] [PMID: 19307458]
[http://dx.doi.org/10.1016/j.intimp.2009.08.001] [PMID: 19666143]
[http://dx.doi.org/10.1016/j.foodchem.2011.06.039]
[http://dx.doi.org/10.1007/s10753-013-9703-2] [PMID: 23892998]
[http://dx.doi.org/10.1016/j.ejphar.2008.01.032] [PMID: 18295200]
[http://dx.doi.org/10.1021/np0205710] [PMID: 12762798]
[http://dx.doi.org/10.1007/s12272-012-0417-z] [PMID: 22553066]
[http://dx.doi.org/10.1016/j.intimp.2011.11.018] [PMID: 22155741]
[http://dx.doi.org/10.1039/C7OB02551C] [PMID: 29164214]
[http://dx.doi.org/10.3181/00379727-218-44309] [PMID: 9714085]
[http://dx.doi.org/10.1007/s10495-015-1198-x] [PMID: 26573275]
[http://dx.doi.org/10.1007/s11655-017-2923-9] [PMID: 29335864]
[http://dx.doi.org/10.1186/s12906-018-2156-2] [PMID: 29530027]
[http://dx.doi.org/10.22074/cellj.2018.5380] [PMID: 29845796]
[http://dx.doi.org/10.20307/nps.2018.24.3.148]
[http://dx.doi.org/10.4062/biomolther.2015.135] [PMID: 27133263]
[http://dx.doi.org/10.3892/mmr.2014.2705] [PMID: 25333675]
[http://dx.doi.org/10.1016/S0304-3940(01)02028-6] [PMID: 11489548]
[http://dx.doi.org/10.1089/jmf.2006.143] [PMID: 17651055]
[http://dx.doi.org/10.1016/j.intimp.2004.08.008] [PMID: 15589480]
[http://dx.doi.org/10.1371/journal.pone.0064372] [PMID: 23691207]
[http://dx.doi.org/10.1046/j.1471-4159.2001.00465.x] [PMID: 11520904]
[http://dx.doi.org/10.1007/BF02976694] [PMID: 12785733]
[PMID: 11270996]
[http://dx.doi.org/10.1038/sj.bjp.0702785] [PMID: 10510444]
[PMID: 27746872]
[http://dx.doi.org/10.1007/s00210-009-0466-0] [PMID: 19904526]
[http://dx.doi.org/10.4162/nrp.2015.9.2.123] [PMID: 25861417]
[http://dx.doi.org/10.1016/j.brainres.2015.10.010] [PMID: 26471408]
[http://dx.doi.org/10.1016/j.bbrc.2006.06.149] [PMID: 16843440]
[http://dx.doi.org/10.1006/excr.1994.1020] [PMID: 8269990]
[http://dx.doi.org/10.1002/(SICI)1098-1136(199802)22:2<138:AID-GLIA5>3.0.CO;2-3] [PMID: 9537834]
[http://dx.doi.org/10.1186/s12906-017-1880-3] [PMID: 28716085]
[http://dx.doi.org/10.1007/s12017-016-8411-0] [PMID: 27209361]
[http://dx.doi.org/10.1007/BF02980029] [PMID: 14609132]
[http://dx.doi.org/10.1016/j.intimp.2016.03.022] [PMID: 27032067]
[http://dx.doi.org/10.1007/s11655-018-2936-4] [PMID: 30090976]
[http://dx.doi.org/10.1007/s11010-016-2655-8] [PMID: 26838169]
[http://dx.doi.org/10.1016/j.biopha.2017.01.152] [PMID: 28178617]
[http://dx.doi.org/10.1055/s-0037-1608480]
[http://dx.doi.org/10.1051/e3sconf/20197801011]
[http://dx.doi.org/10.22452/mjs.vol36no3.2]
[http://dx.doi.org/10.1007/s11064-017-2301-1] [PMID: 28512713]
[http://dx.doi.org/10.3390/ijms17020255] [PMID: 26907256]
[http://dx.doi.org/10.15430/JCP.2018.23.3.134] [PMID: 30370258]
[http://dx.doi.org/10.4103/0973-1296.160466] [PMID: 26246745]
[http://dx.doi.org/10.4162/nrp.2018.12.1.13] [PMID: 29399292]
[http://dx.doi.org/10.4149/gpb-2018044] [PMID: 30806632]
[http://dx.doi.org/10.1155/2019/7585896] [PMID: 31057653]
[http://dx.doi.org/10.1002/cbdv.201700231] [PMID: 28805952]
[http://dx.doi.org/10.1096/fasebj.2019.33.1_supplement.5015]
[http://dx.doi.org/10.1039/C7FO01442B] [PMID: 29354820]
[http://dx.doi.org/10.1016/j.neuint.2015.12.010] [PMID: 26724567]
[http://dx.doi.org/10.1089/jmf.2016.3732] [PMID: 27845863]
[http://dx.doi.org/10.3892/ijmm.2018.3993] [PMID: 30483725]
[http://dx.doi.org/10.4314/tjpr.v16i6.11]
[http://dx.doi.org/10.4103/pm.pm_197_18]
[http://dx.doi.org/10.1016/j.phymed.2016.10.007] [PMID: 27823627]
[http://dx.doi.org/10.3390/molecules200713041] [PMID: 26205049]
[http://dx.doi.org/10.1016/j.foodchem.2016.06.068] [PMID: 27451156]
[http://dx.doi.org/10.3892/ijmm.2014.2020] [PMID: 25483920]
[http://dx.doi.org/10.1016/j.ejphar.2016.02.013] [PMID: 26852953]
[http://dx.doi.org/10.3904/kjim.2014.29.1.31] [PMID: 24574831]
[http://dx.doi.org/10.1016/j.biopha.2016.07.020] [PMID: 27470568]
[http://dx.doi.org/10.1080/02688690209168362] [PMID: 12617238]
[http://dx.doi.org/10.1055/s-2004-835843] [PMID: 15643549]
[http://dx.doi.org/10.1016/S0378-8741(99)00143-9] [PMID: 10661882]
[http://dx.doi.org/10.1016/S0955-2863(02)00190-0] [PMID: 12165361]
[http://dx.doi.org/10.1016/S0753-3322(03)00095-7] [PMID: 14499177]
[http://dx.doi.org/10.1007/s00210-003-0822-4] [PMID: 14673511]
[http://dx.doi.org/10.1186/1472-6882-4-11] [PMID: 15310392]
[http://dx.doi.org/10.1078/094471103321659861] [PMID: 12725569]
[http://dx.doi.org/10.1159/000045471] [PMID: 10461034]
[http://dx.doi.org/10.1016/j.fitote.2005.06.003] [PMID: 16257496]
[http://dx.doi.org/10.1142/s0192415x04001795] [PMID: 15154286]
[http://dx.doi.org/10.3389/fnene.2010.00131] [PMID: 21031160]