13-Acetoxysarcocrassolide Induces Apoptosis in Human Hepatocellular Carcinoma Cells Through Mitochondrial Dysfunction and Suppression of the PI3K/AKT/mTOR/p70S6K Signaling Pathway

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题名:	13-Acetoxysarcocrassolide Induces Apoptosis in Human Hepatocellular Carcinoma Cells Through Mitochondrial Dysfunction and Suppression of the PI3K/AKT/mTOR/p70S6K Signaling Pathway
作者:	Hsu, Chang-Min;Lin, Jen-Jie;Liu, Jui-Hsin Su & Chih-I
贡献者:	健康暨護理學院
关键词:	Biological activity;anti-proliferative;Sarcophyton crassocaule;cancer
日期:	2023-08
上传时间:	2023-08-21T02:52:06Z (UTC)
摘要:	Context: 13-Acetoxysarcocrasside, isolated from the Taiwanese soft coral Sarcophyton crassocaule Moser(Alcyoniidae), has biological activity and induces apoptosis in hepatocellular carcinoma cells. Objective: To elucidate the mechanisms underlying apoptosis induced by 13-acetoxysarcocrasside in HA22T and HepG2 hepatocellular carcinoma cells. Material and methods: MTT and morphology assays were employed to assess the anti-proliferative effects of 13-acetoxysarcocrasside (1–5 lM). TUNEL/DAPI staining and annexin V-fluorescein isothiocyanate/propidium iodide staining were used to detect apoptosis. Cells were treated with13-acetoxysarcocrassolide (0, 1, 2, and 4 lM) for 24 h, and the mechanism of cells apoptotic was detected by western blotting. Cells treated with DMSO were the control. Results: Survival of the cells decreased with the addition of 13-acetoxysarcocrassolide, and at 4 lM cell survival was inhibited by approximately 40%. After treatment of cells with 13-acetoxysarcocrassolide, the incidence of early/late apoptosis to be 0.3%/0.5%5.4%/22.7% for HA22T cells, in the HePG2 cells were 0.6%/0.2%14.4%/23.7%. Western blotting analysis showed that the expression of Bax, Bad, cleaved caspase 3, cleaved caspase 9, cleaved-PARP-1, cytochrome c, and p-4EBP1 increased with an increasing concentration of 13-acetoxysarcocrasside (0, 1, 2, and 4 lM), whereas that of Bcl-2, Bcl-xL, Mcl-1, p-Bad, p-PI3K, p-AKT, p-mTOR, p-70S6K, p-S6, p-eIF4E, and p-eIF4B decreased. Discussion and conclusion: Apoptosis induced by 13-acetoxysarcocrassolide in HA22T and HepG2 cells is mediated by mitochondrial dysfunction and inactivation of the PI3K/AKT/mTOR/p70S6K pathway. The potential of 13-acetoxysarcocrassolide as a chemotherapeutic agent should be further assessed for use in human hepatocellular carcinoma treatment.
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