Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation
|Maki Katamura1, Eri Iwai-Kanai2, Mikihiko Nakaoka1, Yoshifumi Okawa1, Makoto Ariyoshi1, Yuichiro Mita1, Akihiro Nakamura1,
Koji Ikeda1, Takehiro Ogata1, Tomomi Ueyama1 and Satoaki Matoba1*
|1Department of Cardiovascular Medicine, Graduated School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan|
|2Faculty of Health Care, Tenri Health Care University, Bessho-cho, Tenri, Japan|
|Corresponding Author :||Satoaki Matoba
Department of Cardiovascular Medicine
Graduated School of Medical Science
Kyoto Prefectural University of Medicine
465 Kajii-cho Kawaramachi-Hirokoji
Kamigyo-ku, Kyoto, 602 8566, Japan
E-mail: [email protected]
|Received August 14, 2014; Accepted September 29, 2014; Published October 10, 2014|
|Citation: Katamura M, Iwai-Kanai E, Nakaoka M, Okawa Y, Ariyoshi M, et al. (2014) Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation. J Clin Exp Cardiolog 5:337. doi:10.4172/2155-9880.1000337|
|Copyright: © 2014 Katamura M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Related article at
Pubmed Scholar Google
Background and Objective: Doxorubicin (DOX) has been used in cancer therapy for several decades. However, cardiac complications induced by DOX dose-dependently limit the clinical implication at optimal antitumor efficacy. Curcumin (Cur), a natural compound, has been effective as an anticancer agent in various types of cancers. It also protects against cardiac hypertrophy and heart failure, though its effect on cardiomyopathy caused by DOX treatment is unclear. To elucidate the role of curcumin on heart failure, we used the DOX induced cardiomyopathy model and primary cultured cardiac myocytes.
Method and Results: Male C57/BL6 mice were randomized to 4 courses of treatment administered for 4 weeks: Phosphate-Buffered Saline (PBS), Cur, DOX, and DOX+Cur. DOX-treated mice exhibited severe cardiac dysfunction, and the mortality was higher than that in PBS-treated mice. In DOX-treated mice, the number of apoptotic cardiac myocytes was higher and the fibrotic areas were larger than in PBS-treated mice. The cardiotoxic effects of DOX were ameliorated by treatment with Cur. In DOX-treated GFP-LC3 transgenic mice, Cur induced autophagy and decreased apoptosis in the heart. Cur also induced autophagy and suppressed DOX-induced apoptosis in neonatal rat cardiac myocytes. Inhibition of autophagy by 3-methyladenine decreased the cardioprotective effect of Cur. Furthermore, Cur decreased c-Jun N-terminal kinase (JNK) phosphorylation, resulting in reduction of apoptosis. The JNK inhibitor SP600125 abolished these effects.
Conclusion: Cur protects the heart from DOX-induced cardiotoxicity by inducing autophagy and decreasing cardiomyocyte apoptosis. The mechanism involves JNK-mediated modification of apoptosis. Induction of cardiac autophagy may be a novel therapeutic approach for preventing DOX-induced cardiotoxicity.