Document Detail

Oridonin induced autophagy in human cervical carcinoma HeLa cells through Ras, JNK, and P38 regulation.
MedLine Citation:
PMID:  18094523     Owner:  NLM     Status:  MEDLINE    
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.
Qiao Cui; Shin-Ichi Tashiro; Satoshi Onodera; Mutsuhiko Minami; Takashi Ikejima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  105     ISSN:  1347-8613     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-20     Completed Date:  2008-05-05     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  317-25     Citation Subset:  IM    
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, PR China.
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MeSH Terms
Adenine / analogs & derivatives,  pharmacology
Anthracenes / pharmacology
Apoptosis Regulatory Proteins / metabolism
Autophagy / drug effects*
Blotting, Western
Cadaverine / analogs & derivatives,  chemistry,  metabolism
Diterpenes / chemistry,  isolation & purification,  pharmacology*
Diterpenes, Kaurane / chemistry,  pharmacology*
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism
Flavonoids / pharmacology
Flow Cytometry
HeLa Cells
Imidazoles / pharmacology
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Membrane Proteins / metabolism
Microtubule-Associated Proteins / metabolism
Polyenes / pharmacology
Polyunsaturated Alkamides / pharmacology
Pyridines / pharmacology
Rabdosia / chemistry
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
ras Proteins / metabolism*
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Anthracenes; 0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Diterpenes; 0/Diterpenes, Kaurane; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Imidazoles; 0/Membrane Proteins; 0/Microtubule-Associated Proteins; 0/Polyenes; 0/Polyunsaturated Alkamides; 0/Pyridines; 0/SB 203580; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 0/light chain 3, human; 0APJ98UCLQ/oridonin; 10121-91-2/monodansylcadaverine; 462-94-2/Cadaverine; 5142-23-4/3-methyladenine; 52665-74-4/manumycin; 73-24-5/Adenine; EC Signal-Regulated MAP Kinases; EC Mitogen-Activated Protein Kinases; EC Mitogen-Activated Protein Kinases; EC Proteins

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