Induction of several cytochrome P450 genes by doxorubicin in H9c2 cells |
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| Affiliation: | 1. Department of Biomaterials Science and Engineering, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea;2. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea;3. Department of Physiology, Institute of Functional Genomics, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, Republic of Korea;4. Department of Biomedical Chemistry, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea;5. Department of Biomedical Laboratory Science, Kyungbok University, Sinbuk-myeon, Pochen, Gyeonggi 487-717, Republic of Korea;6. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea;1. BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, South Korea;2. College of Pharmacy, The Catholic University of Korea, Bucheon, 14662, South Korea;3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, South Korea;4. Department of Pharmacology, School of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju-si, Gyeongsangbuk-do 38066, Republic of Korea;1. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building, Biocant Park, 3060-197 Cantanhede, Portugal;2. Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, USA |
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| Abstract: | Doxorubicin is a potent anti-neoplastic antibiotic used to treat a wide variety of malignancies; however, its use is limited by dose dependent cardiotoxicity. There is indirect evidence suggesting that doxorubicin cardiotoxicity is CYP-mediated. In the current study, we investigated the effect of doxorubicin on hypertrophic markers, and different CYP gene expression in cardiac derived H9c2 cells. H9c2 cells were incubated with increasing concentrations of doxorubicin and the expressions of different genes were determined by real-time PCR. Our results demonstrate that multiple CYP genes are expressed in H9c2 cells and the level of expression from the highest to the lowest were; CYP1B1, CYP2B1, CYP2J3, CYP1A1, CYP2C11, CYP2C23, CYP2E1, CYP1A2, and CYP2B2. Doxorubicin treatment caused an induction of the hypertrophic markers, ANP and BNP. In addition, doxorubicin caused a significant induction of CYP1A1, CYP1A2, CYP1B1, CYP2B2, CYP2E1, and CYP2J3 gene expression in a concentration-dependent manner. However, only the highest concentration tested, 10 μM, caused an induction of CYP2C11; whereas, CYP2B1 and CYP2C23 were not altered. Our findings demonstrate that doxorubicin induces the hypertrophic markers, ANP and BNP as well as several CYP genes in H9c2 cells. Doxorubicin-mediated CYP induction may represent a novel mechanism by which this drug induces cardiotoxicity. |
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