Tanshinone IIA protects neonatal rat cardiomyocytes from adriamycin-induced apoptosis.
Tanshinone IIA (TSN) is a monomer extracted from the Chinese herb Danshen. In this study, we examined the effect of Tanshinone IIA on adriamycin (ADR)-induced apoptosis in neonatal rat cardiomyocytes and underlying molecular mechanisms. Primary cultured cardiomyocytes were treated with 1 micromol/L of adriamycin for 24 h with or without pretreatment with Tanshinone IIA (0.5-2 micromol/L) for 2 h. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, and flow cytometry measurement were used to assess cell viability and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and dihydroethidium were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the expression of Bcl-2 and Bax proteins. Adriamycin significantly induced apoptosis in cardiomyocytes. Tanshinone IIA (0.5-2 micromol/L) ameliorated apoptosis induced by adriamycin in a dose-dependent manner. Tanshinone IIA (2 micromol/L) markedly attenuated adriamycin-induced reactive oxygen species production. Western blotting revealed that Tanshinone IIA prevented the adriamycin-mediated reduction of the ratio of Bcl-2/Bax. In conclusion, Tanshinone IIA significantly inhibits adriamycin-induced cardiomyocyte apoptosis in a dose-dependent manner, and this effect is at least partly caused by its antioxidant properties.
Gao
Jie
J
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
Yang
Guoqing
G
Pi
Rongbiao
R
Li
Ruifang
R
Wang
Ping
P
Zhang
Huijie
H
Le
Kang
K
Chen
Shaorui
S
Liu
Peiqing
P
D045784:Abietanes; D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018890:Chemoprevention; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005562:Formazans / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D045784:Abietanes; D000970:Antineoplastic Agents; D000975:Antioxidants; C494828:Bax protein, rat; D004365:Drugs, Chinese Herbal; D005562:Formazans; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D051028:bcl-2-Associated X Protein; C021751:tanshinone; D019938:Cyclin D1; C079782:MTT formazan; D004317:Doxorubicin