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dc.contributor.authorGanapathy, Suthakaren_US
dc.contributor.authorChen, Qingheen_US
dc.contributor.authorSingh, Karan P.en_US
dc.contributor.authorShankar, Sharmilaen_US
dc.contributor.authorSrivastava, Rakesh K.en_US
dc.date.accessioned2018-11-09T20:22:02Z
dc.date.available2018-11-09T20:22:02Z
dc.date.issued2010-12-28en_US
dc.identifier.othere15627en_US
dc.identifier.urihttp://hdl.handle.net/10919/85812
dc.description.abstractBackground Resveratrol (3, 4′, 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. Methodology/Principal Findings Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27/K IP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. Conclusions/Significance These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsCreative Commons Attribution 4.0 Internationalen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleResveratrol Enhances Antitumor Activity of TRAIL in Prostate Cancer Xenografts through Activation of FOXO Transcription Factoren_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0015627en_US
dc.identifier.volume5en_US
dc.identifier.issue12en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid21209944en_US
dc.identifier.eissn1932-6203en_US


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International