Down-regulation of deacetylase HDAC6 inhibits the melanoma cell line A375.S2 growth through ROS-dependent mitochondrial pathway

PloS One
Jun BaiLi He

Abstract

Previous studies have shown that histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer. However, its biological roles in the development of melanoma remain unexplored. Our aim was to investigate whether HDAC6 has a biological role in human melanoma development and to understand its underlying mechanism. In the present study, HDAC6 expression was up-regulated in melanoma tissues and cell lines. Knockdown of HDAC6 significantly inhibited the proliferation and colony formation ability of A375.S2 cells, promoted cell arrest at G0/G1 phase and apoptosis. Additionally, western blotting assay showed that HDAC6 silencing suppressed Bcl-2 level and enhanced Bax level, then activated caspase-9 and caspase-3, and further activated the release of cytochrome c from mitochondria to cytoplasm, finally induced cell apoptosis involving the mitochondrial pathway. Knockdown of HDAC6 triggered a significant generation of ROS and disruption of mitochondrial membrane potential (MMP). Furthermore, ROS inhibitor, NAC reduced HDAC6 siRNA-induced ROS production, and blocked HDAC6 siRNA-induced loss of MMP and apoptosis. NAC also significantly blocked HDAC6 siRNA-induced mtDNA copy number decrease and mitochondri...Continue Reading

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Citations

Nov 13, 2015·European Journal of Medicinal Chemistry·Jia-Nian ChenHeng-Shan Wang
Oct 30, 2018·Journal of Cellular Physiology·Hui WangLiping Bai
Sep 13, 2019·Science Translational Medicine·Ann LinJason M Sheltzer
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Jul 15, 2020·Antioxidants·Hossameldin AbouhishManuela Bartoli
Jan 6, 2017·American Journal of Physiology. Renal Physiology·Yingfeng ShiNa Liu
Jun 18, 2016·Pigment Cell & Melanoma Research·Zackie AktaryLionel Larue

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Methods Mentioned

BETA
PCR
flow cytometry
Protein Assay
transfection
FACS

Software Mentioned

Quantity One
FloMax

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