Document Detail


Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, caspase 12 and GADD153 protein expression.
MedLine Citation:
PMID:  20664954     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tanshinone IIA (Tan-IIA) is extracted from Danshen, Salviae miltiorrhizae Radix, which has been widely adopted in traditional herbal medicine to treat cardiovascular and hepatic diseases. Tan-IIA induces apoptosis and inhibits proliferation in human hepatocellular carcinoma (HCC) cells. However, the molecular mechanisms of Tan-IIA on human HCC cells are not understood clearly. In the present study, the cytotoxicity of Tan-IIA as well as its molecular mechanisms in human HCC J5 cells was investigated. The cytotoxicity was assayed by MTT. The protein expression of p53, p21, Bax, Bcl-2, Cdc25c, Cdc2, calreticulin, caspase 12, GADD153, caspase 3 and beta-actin in J5 cells were determined by Western blotting. The cell cycles were analyzed by FACS. The protein expression of caspase 12, GADD1533 and caspase 3 were detected by immunocytochemical staining. The results showed that Tan-IIA inhibited J5 cells in a dose- and time-dependent manner. The protein expression of p53, p21, Bax, calreticulin, caspase 12, caspase 3 and GADD153 were increased, but Bcl-2, Cdc25c and Cdc2 were decreased in J5 cells. In addition, the results also showed that Tan-IIA arrested J5 cells in the G2/M phase. Immunocytochemistry staining showed that J5 cells treated with Tan-IIA up-regulated the protein expression of caspase 12, 3 and GADD153. Taken together, the findings suggest that Tan-IIA inhibits and induces apoptosis in J5 cells through novel molecular targets, calreticulin, caspase 12 and GADD153.
Authors:
Chun-Yuan Cheng; Chin-Cheng Su
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  26     ISSN:  1791-244X     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  379-85     Citation Subset:  IM    
Affiliation:
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Chloromethyl Ketones / metabolism
Animals
Antineoplastic Agents, Phytogenic / pharmacology*,  therapeutic use
Apoptosis / drug effects
Calreticulin / metabolism*
Carcinoma, Hepatocellular / drug therapy*
Caspase 12 / antagonists & inhibitors,  metabolism*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cysteine Proteinase Inhibitors / metabolism
Drugs, Chinese Herbal / pharmacology,  therapeutic use
Humans
Liver Neoplasms / drug therapy*
Male
Mitochondria / metabolism
Phenanthrenes / pharmacology*,  therapeutic use
Transcription Factor CHOP / metabolism*
Chemical
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Antineoplastic Agents, Phytogenic; 0/Calreticulin; 0/Cysteine Proteinase Inhibitors; 0/Drugs, Chinese Herbal; 0/Phenanthrenes; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 147336-12-7/Transcription Factor CHOP; 568-73-0/tanshinone; EC 3.4.22.-/Caspase 12

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