title: 3,3'-Diindolymethane ameliorates adriamycin-induced cardiac fibrosis via activation of a BRCA1-dependent anti-oxidant pathway.
abstract: The cardiotoxicity of adriamycin greatly limits its application in the treatment of cancer. Heart failure that is caused by adriamycin-treatment induced cardiac fibrosis is a major cause of death in patients who are treated with this medication. The severe oxidative stress that is induced by adriamycin is considered to be one of the primary mechanisms by which fibrogenesis of cardiac tissue occurs. In the present study, we demonstrate that 3,3'-diindolymethane (DIM) exhibits a significant anti-fibrosis effect on cardiac tissue in an animal model of adriamycin-induced cardiac fibrosis (AICF). Further studies demonstrated that DIM is able to dramatically up-regulate the expression of breast cancer type 1 susceptibility protein (BRCA1) in cardiac tissue and fibroblast, which subsequently activate the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The upregulation of this transcription factor resulted in the expression of several anti-oxidant genes in the cell. Because DIM is a safe food additive that has been used for decades, our findings suggest that there is a great potential for this chemical to be developed into a clinical medication for the treatment of adriamycin-induced heart failure during cancer therapy.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Zhengwei
authors: Z
authors: Yao
authors: Wei
authors: W
authors: Hu
authors: Shan
authors: S
authors: Yin
authors: Zhen
authors: Z
authors: Huang
authors: Qian
authors: Q
authors: Zhu
authors: Jiangning
authors: J
authors: Chen
authors: Yuhui
authors: Y
authors: Zang
authors: Lei
authors: L
authors: Dong
authors: Junfeng
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D019313:BRCA1 Protein; D007211:Indoles; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C016392:3,3'-diindolylmethane