Oridonin Induced Autophagy in Human Cervical Carcinoma HeLa Cells Through Ras, JNK, and P38 Regulation

Journal of Pharmacological Sciences

Qiao Cui¹  Satoshi Onodera²  Takashi Ikejima¹  Mutsuhiko Minami³  Shin-ichi Tashiro² 

[1] China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, China;Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Japan;Department of Immunology, Yokohama City University School of Medicine, Japan

关键词: oridonin;    autophagy;    Ras;    P38 MAPK;    JNK MAPK;   

DOI  :  10.1254/jphs.FP0070336

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(34)Cited-By(46)In this study, we investigated autophagy induced by oridonin in HeLa cells. HeLa cells were exposed to oridonin, and the fluorescent changes, autophagic levels, and protein expressions were evaluated. Oridonin induced autophagy in HeLa cells in vitro in a dose- and time-dependent manner. Oridonin-treated HeLa cells, which had been prelabeled with the autophagosome-specific dye monodansylcadervarine (MDC), recruited more MDC-positive particles and had a significantly higher fluorescent density; and simultaneously, expressions of autophagy-related proteins, MAP-LC3 and Beclin 1, were increased by oridonin. In oridonin-induced Hela cells, pretreatment with 3-methyladenine (3-MA, the specific inhibitor of autophagy) dose-dependently decreased the autophagic ratio accompanied with downregulation of the protein expressions of MAP-LC3 and Beclin 1. Furthermore, when a Ras inhibitor was applied, the autophagic levels were augmented, whereas P38 and JNK inhibitors decreased the autophagic ratio significantly, indicating that this oridonin-induced autophagic process was negatively regulated by Ras, but positively regulated by P38 and JNK MAPKs. Raf-1 and ERK1/2 had no obvious correlation to these signaling pathways.

【 授权许可】

Unknown