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Article Publish Status: FREE
Abstract Title:

δ-Tocotrienol Induces Human Bladder Cancer Cell Growth Arrest, Apoptosis and Chemosensitization through Inhibition of STAT3 Pathway.

Abstract Source:

PLoS One. 2015 ;10(4):e0122712. Epub 2015 Apr 7. PMID: 25849286

Abstract Author(s):

Changxiao Ye, Wei Zhao, Minghui Li, Junlong Zhuang, Xiang Yan, Qun Lu, Cunjie Chang, Xiaojing Huang, Ji Zhou, Bingxian Xie, Zhen Zhang, Xin Yao, Jun Yan, Hongqian Guo

Article Affiliation:

Changxiao Ye

Abstract:

Vitamin E intake has been implicated in reduction of bladder cancer risk. However, the mechanisms remain elusive. Here we reported thatδ-tocotrienol (δ-T3), one of vitamin E isomers, possessed the most potent cytotoxic capacity against human bladder cancer cells, compared with other Vitamin E isomers. δ-T3 inhibited cancer cell proliferation and colonogenicity through induction of G1 phase arrest and apoptosis. Western blottingassay revealed that δ-T3 increased the expression levels of cell cycle inhibitors (p21, p27), pro-apoptotic protein (Bax) and suppressed expression levels of cell cycle protein (Cyclin D1), anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1), resulting in the Caspase-3 activation and cleavage of PARP. Moreover, the δ-T3 treatment inhibited ETK phosphorylation level and induced SHP-1 expression, which was correlated with downregulation of STAT3 activation. In line with this, δ-T3 reduced the STAT3 protein level in nuclear fraction, as well as its transcription activity. Knockdown of SHP-1 partially reversed δ-T3-induced cell growth arrest. Importantly, low dose of δ-T3 sensitized Gemcitabine-induced cytotoxic effects on human bladder cancer cells. Overall, our findings demonstrated, for the first time, the cytotoxic effects of δ-T3 on bladder cancer cells and suggest that δ-T3 mightbe a promising chemosensitization reagent for Gemcitabine in bladder cancer treatment.

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Sayer Ji
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Easy Turmeric recipes + The Dark Side of Wheat

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