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Kavalactone yangonin induces autophagy and sensitizes bladder cancer cells to flavokawain A and docetaxel via inhibition of the mTOR pathway

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The Journal of Biomedical Research 2017年第5期31卷 408-418页

作者： Zhongbo Liu U-Syn Ha Ke Yu Chunli Wu Noriko Yokoyama Xiaolin Zi Departments of Urology University of CaliforniaIrvine Orange CA 92868 USA. Pharmacology University of CaliforniaIrvine Orange CA 92868 USA. Chao Family Comprehensive Cancer Center University of CaliforniaIrvine Orange CA 92868 USA.

Consumption of kava(Piper methysticum Forst) has been linked to reduced cancer risk in the South Pacific *** are major bioactive components in kava root extracts, which have recently demonstrated anti-cancer activities. However, molecular mechanisms of kavalactones' anti-cancer action remain largely unknown. We have identified two kavalactones, yangonin and 5' 6'-dehydrokawain, as potent inducers of autophagic cell death in bladder cancer cells. The effect of yangonin inducing autophagy is associated with increased expression of beclin and *** addition, yangonin increases the expression of LKB1 and decreases the phosphorylation of Akt, PRAS40, rpS6,p70S6 K and 4E-BP1, leading to increased binding of 4E-BP1 to m7 GTP. The growth inhibitory effects of yangonin were attenuated in TSC1 or LKB1 knockout mouse embryonic fibroblasts, suggesting that TSC1 and LKB1 expression may contribute to optimal growth inhibition by yangonin. Furthermore, yangonin reduces the viability of bladder cancer cell lines derived from different stages of human bladder cancer, and acts synergistically with apoptosis-inducing agents such as docetaxel and flavokawain A. Our results support a novel anti-bladder cancer mechanism by yangonin and further studies are needed to assess the potential use of yangonin for bladder cancer prevention and treatment

关键词： yangonin bladder cancer autophagy mTOR

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