Tags

Type your tag names separated by a space and hit enter

Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation.
J Cell Biochem. 2011 Oct; 112(10):2873-81.JC

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 (10 µM) 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 (25 µM) and doxorubicin for 24 h significantly reduced both ROS generation (587 ± 89 a.u. vs. 932 a.u. ± 121 a.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 (10 µM; 24 h) 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.

Authors+Show Affiliations

Emergency Resuscitation Center, Section of Emergency Medicine, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21618589

Citation

Chang, Wei-Tien, et al. "Baicalein Protects Against Doxorubicin-induced Cardiotoxicity By Attenuation of Mitochondrial Oxidant Injury and JNK Activation." Journal of Cellular Biochemistry, vol. 112, no. 10, 2011, pp. 2873-81.
Chang WT, Li J, Haung HH, et al. Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation. J Cell Biochem. 2011;112(10):2873-81.
Chang, W. T., Li, J., Haung, H. H., Liu, H., Han, M., Ramachandran, S., Li, C. Q., Sharp, W. W., Hamann, K. J., Yuan, C. S., Hoek, T. L., & Shao, Z. H. (2011). Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation. Journal of Cellular Biochemistry, 112(10), 2873-81. https://doi.org/10.1002/jcb.23201
Chang WT, et al. Baicalein Protects Against Doxorubicin-induced Cardiotoxicity By Attenuation of Mitochondrial Oxidant Injury and JNK Activation. J Cell Biochem. 2011;112(10):2873-81. PubMed PMID: 21618589.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation. AU - Chang,Wei-Tien, AU - Li,Jing, AU - Haung,Hsien-Hao, AU - Liu,Huiping, AU - Han,Mei, AU - Ramachandran,Srinivasan, AU - Li,Chang-Qing, AU - Sharp,Willard W, AU - Hamann,Kimm J, AU - Yuan,Chun-Su, AU - Hoek,Terry L Vanden, AU - Shao,Zuo-Hui, PY - 2011/5/28/entrez PY - 2011/5/28/pubmed PY - 2012/4/13/medline SP - 2873 EP - 81 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 112 IS - 10 N2 - 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 (10 µM) 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 (25 µM) and doxorubicin for 24 h significantly reduced both ROS generation (587 ± 89 a.u. vs. 932 a.u. ± 121 a.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 (10 µM; 24 h) 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. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/21618589/Baicalein_protects_against_doxorubicin_induced_cardiotoxicity_by_attenuation_of_mitochondrial_oxidant_injury_and_JNK_activation_ L2 - https://doi.org/10.1002/jcb.23201 DB - PRIME DP - Unbound Medicine ER -