title: Tanshinone IIA prevents doxorubicin-induced cardiomyocyte apoptosis through Akt-dependent pathway.
abstract: BACKGROUND
  Doxorubicin, one of the original anthracyclines, remains among the most effective anticancer drugs ever developed. Clinical use of doxorubicin is, however, greatly limited by its serious adverse cardiac effects that may ultimately lead to cardiomyopathy and heart failure. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as 'Danshen' in traditional Chinese medicine for treating cardiovascular disorders. The objective of this study was set to evaluate the protective effect of tanshinone IIA on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s).
  
  
  METHODS
  Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 μM), tanshinone IIA (0.1, 0.3, 1 and 3 μM), or tanshinone IIA plus doxorubicin.
  
  
  RESULTS
  We found that tanshinone IIA (1 and 3 μM) inhibited doxorubicin-induced reactive oxygen species generation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased BcL-x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, Akt phosphorylation was enhanced by tanshinone IIA treatment in cardiomyocytes. The wortmannin (100 nM), LY294002 (10 nM), and siRNA transfection for Akt significantly reduced tanshinone IIA-induced protective effect.
  
  
  CONCLUSIONS
  These findings suggest that tanshinone IIA protects cardiomyocytes from doxorubicin-induced apoptosis in part through Akt-signaling pathways, which may potentially protect the heart from the severe toxicity of doxorubicin.
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Hong-Jye
authors.initials: HJ
authors.lastname: Hong
authors.forename: Ju-Chi
authors.initials: JC
authors.lastname: Liu
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Jin-Jer
authors.initials: JJ
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D045784:Abietanes; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; C021751:tanshinone; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt