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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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General Research Article

Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma

Author(s): Pratibha Pandey, Preeti Bajpai*, Mohammad H. Siddiqui, Uzma Sayyed, Rohit Tiwari, Rafia Shekh, Kumudesh Mishra and V.K. Kapoor

Volume 19, Issue 6, 2019

Page: [826 - 837] Pages: 12

DOI: 10.2174/1871530319666190206124120

Price: $65

Abstract

Background: Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.

Objective: In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.

Methods: In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.

Results: Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.

Conclusion: Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

Keywords: Stigmasterol, apoptosis, gall bladder cancer, caspase-3, therapeutics, Jab1 gene.

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[1]
Lopaczynski, W.; Zeisel, S.H. Antioxidants, programmed cell death, and cancer. Nutr. Res., 2001, 21(1-2), 295-307.
[http://dx.doi.org/10.1016/S0271-5317(00)00288-8]
[2]
von Schwarzenberg, K.; Vollmar, A.M. Targeting apoptosis pathways by natural compounds in cancer: marine compounds as lead structures and chemical tools for cancer therapy. Cancer Lett., 2013, 332(2), 295-303.
[http://dx.doi.org/10.1016/j.canlet.2010.07.004] [PMID: 20673697]
[3]
Khoogar, R.; Kim, B.C.; Morris, J.; Wargovich, M.J. Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: A focus on gastrointestinal cancer. Am. J. Physiol. Gastrointest. Liver Physiol., 2016, 310(9), G629-G644.
[http://dx.doi.org/10.1152/ajpgi.00201.2015] [PMID: 26893159]
[4]
Cragg, G.M.; Newman, D.J. Natural products: a continuing source of novel drug leads. Biochim. Biophys. Acta, 2013, 1830(6), 3670-3695.
[http://dx.doi.org/10.1016/j.bbagen.2013.02.008] [PMID: 23428572]
[5]
Chinembiri, T.N.; du Plessis, L.H.; Gerber, M.; Hamman, J.H.; du Plessis, J. Review of natural compounds for potential skin cancer treatment. Molecules, 2014, 19(8), 11679-11721.
[http://dx.doi.org/10.3390/molecules190811679] [PMID: 25102117]
[6]
Colomer, R.; Sarrats, A.; Lupu, R.; Puig, T. Natural polyphenols and their synthetic analogs as emerging anticancer agents. Curr. Drug Targets, 2017, 18(2), 147-159.
[http://dx.doi.org/10.2174/1389450117666160112113930] [PMID: 26758667]
[7]
Blowman, K.; Magalhães, M.; Lemos, M.F.L.; Cabral, C.; Pires, I.M. Anticancer properties of essential oils and other natural products. Evid. Based Complement. Alternat. Med., 2018. 20183149362
[http://dx.doi.org/http://10.1155/2018/3149362] [PMID: 29765461]
[8]
Nair, P.P.; Turjman, N.; Kessie, G.; Calkins, B.; Goodman, G.T.; Davidovitz, H.; Nimmagadda, G. Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Dietary cholesterol, β-sitosterol, and stigmasterol. Am. J. Clin. Nutr., 1984, 40(4)(Suppl.), 927-930.
[http://dx.doi.org/10.1093/ajcn/40.4.927] [PMID: 6486101]
[9]
Shahzad, N.; Khan, W.; Md, S.; Ali, A.; Saluja, S.S.; Sharma, S.; Al-Allaf, F.A.; Abduljaleel, Z.; Ibrahim, I.A.A.; Abdel-Wahab, A.F.; Afify, M.A.; Al-Ghamdi, S.S. Phytosterols as a natural anticancer agent: Current status and future perspective. Biomed. Pharmacother., 2017, 88, 786-794.
[http://dx.doi.org/10.1016/j.biopha.2017.01.068] [PMID: 28157655]
[10]
von Holtz, R.L.; Fink, C.S.; Awad, A.B. β-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells. Nutr. Cancer, 1998, 32(1), 8-12.
[http://dx.doi.org/10.1080/01635589809514709] [PMID: 9824850]
[11]
Llaverias, G.; Escolà-Gil, J.C.; Lerma, E.; Julve, J.; Pons, C.; Cabré, A.; Cofán, M.; Ros, E.; Sánchez-Quesada, J.L.; Blanco-Vaca, F. Phytosterols inhibit the tumor growth and lipoprotein oxidizability induced by a high-fat diet in mice with inherited breast cancer. J. Nutr. Biochem., 2013, 24(1), 39-48.
[http://dx.doi.org/10.1016/j.jnutbio.2012.01.007] [PMID: 22658647]
[12]
O’Callaghan, Y.C.; Foley, D.A.; O’Connell, N.M.; McCarthy, F.O.; Maguire, A.R.; O’Brien, N.M. Cytotoxic and apoptotic effects of the oxidized derivatives of stigmasterol in the U937 human monocytic cell line. J. Agric. Food Chem., 2010, 58(19), 10793-10798.
[http://dx.doi.org/10.1021/jf1023017] [PMID: 20828195]
[13]
Otto, T.; Sicinski, P. Cell cycle proteins as promising targets in cancer therapy. Nat. Rev. Cancer, 2017, 17(2), 93-115.
[http://dx.doi.org/10.1038/nrc.2016.138] [PMID: 28127048]
[14]
Malumbres, M.; Barbacid, M. Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer, 2009, 9(3), 153-166.
[http://dx.doi.org/10.1038/nrc2602] [PMID: 19238148]
[15]
Sherr, C.J.; Bartek, J. Cell cycle–targeted cancer therapies. Annual Review of Cancer Biology, 2017, 1, 41-57.
[http://dx.doi.org/10.1146/annurev-cancerbio-040716-075628]
[16]
Gérard, C.; Goldbeter, A. The balance between cell cycle arrest and cell proliferation: control by the extracellular matrix and by contact inhibition. Interface Focus, 2014, 4(3)20130075
[http://dx.doi.org/10.1098/rsfs.2013.0075] [PMID: 24904738]
[17]
Donjerkovic, D.; Scott, D.W. Regulation of the G1 phase of the mammalian cell cycle. Cell Res., 2000, 10(1), 1-16.
[http://dx.doi.org/10.1038/sj.cr.7290031] [PMID: 10765979]
[18]
Giacinti, C.; Giordano, A. RB and cell cycle progression. Oncogene, 2006, 25(38), 5220-5227.
[http://dx.doi.org/10.1038/sj.onc.1209615] [PMID: 16936740]
[19]
Pandey, P.; Sayyed, U.; Tiwari, R.; Pathak, N.; Siddiqui, M.H.; Bajpai, P. Anticancer and apoptosis-inducing effects of curcumin against gall bladder carcinoma. Int. J. Pharm. Sci. Res., 2018, 9(1), 68-77.
[20]
Khan, F.; Khan, I.; Farooqui, A.; Ansari, I.A. Carvacrol induces reactive oxygen species (ros)-mediated apoptosis along with cell cycle arrest at g0/g1 in human prostate cancer cells. Nutr. Cancer, 2017, 69(7), 1075-1087.
[http://dx.doi.org/10.1080/01635581.2017.1359321] [PMID: 28872904]
[21]
Farooqui, A.; Khan, F.; Khan, I.; Ansari, I.A. Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G0/G1 in HPV18+ human cervical cancer HeLa cell line. Biomed. Pharmacother., 2018, 97, 752-764.
[http://dx.doi.org/10.1016/j.biopha.2017.10.147] [PMID: 29107932]
[22]
Enari, M.; Sakahira, H.; Yokoyama, H.; Okawa, K.; Iwamatsu, A.; Nagata, S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 1998, 391(6662), 43-50.
[http://dx.doi.org/10.1038/34112] [PMID: 9422506]
[23]
Martin-Cordero, C.; Leon-Gonzalez, A.J.; Calderon-Montano, J.M.; Burgos-Moron, E.; Lopez-Lazaro, M. Pro-oxidant natural products as anticancer agents. Curr. Drug Targets, 2012, 13(8), 1006-1028.
[http://dx.doi.org/10.2174/138945012802009044] [PMID: 22594470]
[24]
Fruehauf, J.P.; Meyskens, F.L. Jr Reactive oxygen species: a breath of life or death? Clin. Cancer Res., 2007, 13(3), 789-794.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2082] [PMID: 17289868]
[25]
Trachootham, D.; Alexandre, J.; Huang, P. Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat. Rev. Drug Discov., 2009, 8(7), 579-591.
[http://dx.doi.org/10.1038/nrd2803] [PMID: 19478820]
[26]
Scaduto, R.C., Jr; Grotyohann, L.W. ScadutoJr. Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys. J., 1999, 76(1 Pt 1), 469-477.
[http://dx.doi.org/10.1016/S0006-3495(99)77214-0] [PMID: 9876159]
[27]
Schieke, S.M.; Phillips, D.; McCoy, J.P., Jr; Aponte, A.M.; Shen, R.F.; Balaban, R.S.; Finkel, T. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J. Biol. Chem., 2006, 281(37), 27643-27652.
[http://dx.doi.org/10.1074/jbc.M603536200] [PMID: 16847060]
[28]
Emaus, R.K.; Grunwald, R.; Lemasters, J.J. Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim. Biophys. Acta, 1986, 850(3), 436-448.
[http://dx.doi.org/10.1016/0005-2728(86)90112-X] [PMID: 2873836]
[29]
Polla, B.S.; Kantengwa, S.; François, D.; Salvioli, S.; Franceschi, C.; Marsac, C.; Cossarizza, A. Mitochondria are selective targets for the protective effects of heat shock against oxidative injury. Proc. Natl. Acad. Sci. USA, 1996, 93(13), 6458-6463.
[http://dx.doi.org/10.1073/pnas.93.13.6458] [PMID: 8692837]
[30]
Duan, S.; Pagano, M. SPOP mutations or ERG rearrangements result in enhanced levels of ERG to promote cell invasion in prostate cancer. Mol. Cell, 2015, 59(6), 883-884.
[http://dx.doi.org/10.1016/j.molcel.2015.09.003] [PMID: 26384661]

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