Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation

Wei Tien Chang, Jing Li, Hsien Hao Haung, Huiping Liu, Mei Han, Srinivasan Ramachandran, Chang Qing Li, Willard W. Sharp, Kimm J. Hamann, Chun Su Yuan, Terry L Vanden Hoek, Zuo Hui Shao

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The cardiotoxicity of doxorubicin limits its clinical use in the treatment of a variety of malignancies. Previous studies suggest that doxorubicin- associated cardiotoxicity is mediated by reactive oxygen species (ROS)-induced apoptosis. We therefore investigated if baicalein, a natural antioxidant component of Scutellaria baicalensis, could attenuate ROS generation and cell death induced by doxorubicin. Using an established chick cardiomyocyte model, doxorubicin (10μM) increased cell death in a concentration- and time-dependent manner. ROS generation was increased in a dose-response fashion and associated with loss of mitochondrial membrane potential. Doxorubicin also augmented DNA fragmentation and increased the phosphorylation of ROS-sensitive pro-apoptotic kinase c-Jun N-terminal kinase (JNK). Adjunct treatment of baicalein (25μM) and doxorubicin for 24h significantly reduced both ROS generation (587±89a.u. vs. 932a.u.±121a.u., P<0.01) and cell death (30.6±5.1% vs. 46.8±8.3%, P<0.01). The dissipated mitochondrial potential and increased DNA fragmentation were also ameliorated. Along with the reduction of ROS and apoptosis, baicalein attenuated phosphorylation of JNK induced by doxorubicin (1.7±0.3 vs. 3.0±0.4-fold, P<0.05). Co-treatment of cardiomyocytes with doxorubicin and JNK inhibitor SP600125 (10μM; 24h) reduced JNK phosphorylation and enhanced cell survival, suggesting that the baicalein protection against doxorubicin cardiotoxicity was mediated by JNK activation. Importantly, concurrent baicalein treatment did not interfere with the anti-proliferative effects of doxorubicin in human breast cancer MCF-7 cells. In conclusion, baicalein adjunct treatment confers anti-apoptotic protection against doxorubicin-induced cardiotoxicity without compromising its anti-cancer efficacy.

Original languageEnglish (US)
Pages (from-to)2873-2881
Number of pages9
JournalJournal of Cellular Biochemistry
Volume112
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • JNK
  • anti-proliferative effect
  • apoptosis
  • baicalein
  • doxorubicin
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation'. Together they form a unique fingerprint.

Cite this