13-Acetoxysarcocrassolide Induces Apoptosis on Human Gastric Carcinoma Cells Through Mitochondria-Related Apoptotic Pathways: p38/JNK Activation and PI3K/AKT Suppression

Marine Drugs

Ching-Chyuan Su⁶  Jeff Yi-Fu Chen¹  Zhong-Hao Din²  Jui-Hsin Su⁸  Zih-Yan Yang⁷  Yi-Jen Chen³  Robert Y.L. Wang⁴  Yu-Jen Wu⁵ 

[1] Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan; E-Mail:;Graduate Institute of Applied Healthy and Biotechnology, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; E-Mail:;Department of Biomedical Sciences and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan;Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan; E-Mail:;Graduate Institute of Food Science, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan; E-Mail:;National Museum of Marine Biology and Aquarium, Pingtung 94446, Taiwan; E-Mail:

关键词: 13-acetoxysarcocrassolide;    soft coral;    gastric cancer cells;    apoptosis;    p38 and JNK pathways;   

DOI  :  10.3390/md12105295

来源: mdpi

【 摘 要 】

13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways.

【 授权许可】

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