Recoding the Cancer Epigenome by Intervening in Metabolism and Iron Homeostasis with Mitochondria-Targeted Rhenium(I) Complexes |
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Authors: | Zheng-Yin Pan Dr. Cai-Ping Tan Lu-Si Rao Hang Zhang Yue Zheng Liang Hao Prof. Liang-Nian Ji Prof. Zong-Wan Mao |
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Affiliation: | MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275 P. R. China |
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Abstract: | The development and malignancy of cancer cells are closely related to the changes of the epigenome. In this work, a mitochondria-targeted rhenium(I) complex ( DFX-Re3 ), integrating the clinical iron chelating agent deferasirox ( DFX ), has been designed. By relocating iron to the mitochondria and changing the key metabolic species related to epigenetic modifications, DFX-Re3 can elevate the methylation levels of histone, DNA, and RNA. As a consequence, DFX-Re3 affects the events related to apoptosis, RNA polymerases, and T-cell receptor signaling pathways. Finally, it is shown that DFX-Re3 induces immunogenic apoptotic cell death and exhibits potent antitumor activity in vivo. This study provides a new approach for the design of novel epigenetic drugs that can recode the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis. |
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Keywords: | anticancer epigenetics drug discovery metabolism rhenium |
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