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PTEN/Akt Signaling-Mediated Activation of the Mitochondrial Pathway Contributes to the 3,3′-Diindolylmethane-Mediated Antitumor Effect in Malignant Melanoma Cells

Journal of Medicinal Food 2020년 23권 12호 p.1248 ~ 1258
Wang Xiaoli, Zhao Yueqiang, Yu Mosheng, Xu Yu,
소속 상세정보
 ( Wang Xiaoli ) - Wuhan University Renmin Hospital Department of Plastic Surgery
 ( Zhao Yueqiang ) - Wuhan University Renmin Hospital Department of Plastic Surgery
 ( Yu Mosheng ) - Wuhan University Renmin Hospital Department of Plastic Surgery
 ( Xu Yu ) - Wuhan University Renmin Hospital Department of Otolaryngology-Head and Neck Surgery

Abstract


3,3′-diindolylmethane (DIM) has an anticancer activity, but the role DIM plays on malignant melanoma cells and its specific mechanism is unclear. We studied the biological effects of DIM on malignant melanoma cells and the related mechanism and the results showed that DIM significantly suppressed cell proliferation and induced apoptosis in malignant melanoma cells. In addition, the expression levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN), Bax, Bid, cleaved caspase-3, and cleaved caspase-9 were increased after DIM treatment. In A2058 PTENmut cells, DIM-mediated inhibition of proliferation and DIM-induced apoptosis were attenuated. Additionally, the overexpression and knockdown of PTEN could regulate such effects of DIM in malignant melanoma cells. Furthermore, DIM exerted growth-inhibiting and apoptosis-inducing effects in vivo. This study demonstrated that DIM has antitumor effect in human malignant melanoma cells through the mitochondrial apoptotic pathway activated by PTEN/Akt signaling.

키워드

apoptosis; DIM; malignant melanoma; proliferation; PTEN

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