α-Mangostin Induces Ca2+-ATPase-Dependent Apoptosis via Mitochondrial Pathway in PC12 Cells

Journal of Pharmacological Sciences

Hisae Oku²  Ayumi Sato¹  Yasushi Ohizumi¹  Hironori Fujiwara¹  Kyoko Ishiguro² 

[1] Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University;School of Pharmaceutical Sciences, Mukogawa Women’s University

关键词: α-mangostin;    xanthone;    apoptosis;    Ca2+-ATPase;    mitochondorial pathway;   

DOI  :  10.1254/jphs.95.33

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(28)We investigated the cell death effects of eight xanthones on PC12 rat pheochromocytoma cells. Among these compounds, α-mangostin, from the fruit hull of Garcinia mangostana L., had the most potent effect with the EC50 value of 4 μM. α-Mangostin-treated PC12 cells demonstrated typical apoptotic DNA fragmentation and caspase-3 cleavage (equivalent to activation). The flow cytometric analysis indicated that this compound induced apoptosis in time-and concentration-dependent manners. α-Mangostin showed the features of the mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and cytochrome c release. Furthermore, α-mangostin inhibited the sarco(endo)plasmic reticulum Ca2+-ATPase markedly. There was a correlation between the Ca2+-ATPase inhibitory effects and the apoptotic effects of the xanthone derivatives. On the other hand, c-Jun NH2-terminal kinase (JNK/SAPK), one of the signaling molecules of endoplasmic reticulum (ER) stress, was activated with α-mangostin treatment. These results suggest that α-mangostin inhibits Ca2+-ATPase to cause apoptosis through the mitochondorial pathway.

【 授权许可】

Unknown