Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan.
Department of Research & Development, Yu Jun Biotechnology Co., Ltd, Pingtung, Taiwan.
Pharm Biol. 2022 Dec;60(1):2276-2285. doi: 10.1080/13880209.2022.2145489.
13-Acetoxysarcocrasside, isolated from the Taiwanese soft coral Moser (Alcyoniidae), has biological activity and induces apoptosis in hepatocellular carcinoma cells.
To elucidate the mechanisms underlying apoptosis induced by 13-acetoxysarcocrasside in HA22T and HepG2 hepatocellular carcinoma cells.
MTT and morphology assays were employed to assess the anti-proliferative effects of 13-acetoxysarcocrasside (1-5 μM). 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 μM) for 24 h, and the mechanism of cells apoptotic was detected by western blotting. Cells treated with DMSO were the control.
Survival of the cells decreased with the addition of 13-acetoxysarcocrassolide, and at 4 μM 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 -4EBP1 increased with an increasing concentration of 13-acetoxysarcocrasside (0, 1, 2, and 4 μM), whereas that of Bcl-2, Bcl-xL, Mcl-1, -Bad, -PI3K, -AKT, -mTOR, -70S6K, -S6, -eIF4E, and -eIF4B decreased.
Apoptosis induced by 13-acetoxysarcocrassolide in HA22T and HepG2 cells is mediated by mitochondrial dysfunction and inactivation of the PI3K/AKT/mTOR/70S6K pathway. The potential of 13-acetoxysarcocrassolide as a chemotherapeutic agent should be further assessed for use in human hepatocellular carcinoma treatment.
从台湾软珊瑚（Alcyoniidae 科）Moser 中分离得到的 13-乙酰基肌醇，具有生物活性，并能诱导肝癌细胞凋亡。
阐明 13-乙酰基肌醇在 HA22T 和 HepG2 肝癌细胞中诱导凋亡的机制。
采用 MTT 和形态学检测评估 13-乙酰基肌醇（1-5 μM）的抗增殖作用。TUNEL/DAPI 染色和 Annexin V-荧光素异硫氰酸酯/碘化丙啶染色用于检测凋亡。用 13-乙酰基肌醇（0、1、2 和 4 μM）处理细胞 24 h，通过 Western blot 检测细胞凋亡的机制。用 DMSO 处理的细胞作为对照。
随着 13-乙酰基肌醇的加入，细胞存活率下降，4 μM 时细胞存活率抑制约 40%。用 13-乙酰基肌醇处理细胞后，HA22T 细胞早期/晚期凋亡率分别为 0.3%/0.5%∼5.4%/22.7%，HePG2 细胞分别为 0.6%/0.2%∼14.4%/23.7%。Western blot 分析显示，随着 13-乙酰基肌醇浓度的增加（0、1、2 和 4 μM），Bax、Bad、cleaved caspase 3、cleaved caspase 9、cleaved-PARP-1、细胞色素 c 和-4EBP1 的表达增加，而 Bcl-2、Bcl-xL、Mcl-1、-Bad、-PI3K、-AKT、-mTOR、-70S6K、-S6、-eIF4E 和-eIF4B 的表达减少。
13-乙酰基肌醇诱导 HA22T 和 HepG2 细胞凋亡是通过线粒体功能障碍和 PI3K/AKT/mTOR/70S6K 通路失活介导的。13-乙酰基肌醇作为化疗药物的潜力应进一步评估，以用于人类肝癌的治疗。
