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  • Title: Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades.
    Author: Kim SW, Kim SM, Bae H, Nam D, Lee JH, Lee SG, Shim BS, Kim SH, Ahn KS, Choi SH, Sethi G, Ahn KS.
    Journal: Prostate; 2013 Feb 15; 73(3):296-305. PubMed ID: 22887478.
    Abstract:
    BACKGROUND: Akt/mTOR/S6K1 signaling cascades play an important role both in the survival and proliferation of tumor cells. METHODS: In the present study, we investigated the effects of embelin (EB), identified primarily from the Embelia ribes plant, on the Akt/mTOR/S6K1 activation, associated gene products, cellular proliferation, and apoptosis in human prostate cancer cells. RESULTS: EB exerted significant cytotoxic and suppressive effects on Akt and mTOR activation against androgen-independent PC-3 cells as compared to androgen-dependent LNCaP cells. Moreover, EB suppressed the constitutive activation of Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, down-regulation of anti-apoptotic (Bcl-2, Bcl-xL, survivin, IAP-1, and IAP-2) and proliferative (cyclin D1) proteins, activation of caspase-3, and cleavage of PARP. We also observed that EB can significantly enhance the apoptotic effects of a specific pharmacological Akt inhibitor when used in combination and also caused broad inhibition of all the three kinases in Akt/mTOR/S6K1 signaling axis in PC-3 cells. CONCLUSIONS: EB inhibits multiple signaling cascades involved in tumorigenesis and can be used as a potential therapeutic candidate for both the prevention and treatment of prostate cancer.
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