Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/991
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dc.contributor.authorGupta, Sarika-
dc.contributor.authorTripathi, Rakshamani-
dc.contributor.authorSamadder, Tanmoy-
dc.contributor.authorSurolia, Avadhesha-
dc.contributor.authorShaha, Chandrima-
dc.date.accessioned2017-10-06T10:37:41Z-
dc.date.available2017-10-06T10:37:41Z-
dc.date.issued2011-02-
dc.identifier.urihttp://hdl.handle.net/123456789/991-
dc.description.abstractUse of chemotherapeutic drug cisplatin is limited because of its toxicity. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin to reduce its effective treatment dose. This study evaluates the potential of fisetin, a flavonoid, to increase cisplatin cytotoxicity in human embryonal carcinoma NT2/D1 cells. Addition of fisetin to cisplatin enhanced cisplatin cytotoxicity in vitro at four times lower dose than that required by cisplatin monotherapy for similar cytotoxic effects. Cisplatin, fisetin monotherapy, and addition of fisetin to cisplatin in a combination increased FasL expression. Cisplatin and fisetin as single agents activated caspases-8 and -3 and caspases-9 and -7, respectively, whereas combination treatment activated all 4 caspases. Increases in p53 and p21 and decreases in cyclin B1 and survivin occurred, all effects being more exaggerated with the combination. Fisetin, with or without cisplatin, increased expression of proapoptotic protein Bak and induced its mitochondrial oligomerization. Bid truncation and mitochondrial translocation of Bid and p53 was induced by fisetin in the presence or absence of cisplatin. Downregulation of p53 by short hairpin RNA during drug treatment decreased p21 levels but caused survivin increase, thus reducing cell death. Upstream to p53, inhibition of p38 phosphorylation reduced p53 phosphorylation and cell death. In a NT2/D1 mouse xenograft model, combination therapy was most effective in reducing tumor size. In summary, findings of this study suggest that addition of fisetin to cisplatin activates both the mitochondrial and the cell death receptor pathway and could be a promising regimen for the elimination of embryonal carcinoma cells.en_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.titleAnticancer Activity of a Combination of Cisplatin and Fisetin in Embryonal Carcinoma Cells and Xenograft Tumorsen_US
dc.journalMolecular Cancer Therapeuticsen_US
dc.volumeno10en_US
dc.issueno2en_US
dc.pages255-268en_US
Appears in Collections:Molecular Sciences, Publications

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