Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells

Abstract Metformin (Met) exhibits anticancer ability in various cancer cell lines. This report aims to explore the exact molecular mechanism of Met-induced apoptosis in HCT116 cells, a human colorectal cancer cell line. Met-induced reactive oxygen species (ROS) increase and ROS-dependent cell death...

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Autores principales:	Hongce Chen, Beini Sun, Han Sun, Lingjun Xu, Guihao Wu, Zhuang Tu, Xuecheng Cheng, Xuhong Fan, Zihao Mai, Qiling Tang, Xiaoping Wang, Tongsheng Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/ec5ff3f3032d4cd888f7caf48a7b9838
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spelling	oai:doaj.org-article:ec5ff3f3032d4cd888f7caf48a7b98382021-11-28T12:10:41ZBak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells10.1038/s41420-021-00755-y2058-7716https://doaj.org/article/ec5ff3f3032d4cd888f7caf48a7b98382021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00755-yhttps://doaj.org/toc/2058-7716Abstract Metformin (Met) exhibits anticancer ability in various cancer cell lines. This report aims to explore the exact molecular mechanism of Met-induced apoptosis in HCT116 cells, a human colorectal cancer cell line. Met-induced reactive oxygen species (ROS) increase and ROS-dependent cell death accompanied by plasma membrane blistering, mitochondrial swelling, loss of mitochondrial membrane potential, and release of cytochrome c. Western blotting analysis showed that Met upregulated Bak expression but downregulated Bax expression. Most importantly, silencing Bak instead of Bax inhibited Met-induced loss of mitochondrial membrane potential, indicating the key role of Bak in Met-induced apoptosis. Live-cell fluorescence resonance energy transfer (FRET) analysis showed that Met unlocked the binding of Mcl-1 to Bak, and enhanced the binding of Bim to Bak and subsequent Bak homo-oligomerization. Western blotting analysis showed that Met enhanced AMPK phosphorylation and Bim expression, and compound C, an inhibitor of AMPK, inhibited Met-induced Bim upregulation. Although Met increased the expression of Bcl-xL, overexpression of Bcl-xL did not prevent Met-induced apoptosis. In summary, our data demonstrate for the first time that Met promotes ROS-dependent apoptosis by regulating the Mcl-1-Bim-Bak axis.Hongce ChenBeini SunHan SunLingjun XuGuihao WuZhuang TuXuecheng ChengXuhong FanZihao MaiQiling TangXiaoping WangTongsheng ChenNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Hongce Chen Beini Sun Han Sun Lingjun Xu Guihao Wu Zhuang Tu Xuecheng Cheng Xuhong Fan Zihao Mai Qiling Tang Xiaoping Wang Tongsheng Chen Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells
description	Abstract Metformin (Met) exhibits anticancer ability in various cancer cell lines. This report aims to explore the exact molecular mechanism of Met-induced apoptosis in HCT116 cells, a human colorectal cancer cell line. Met-induced reactive oxygen species (ROS) increase and ROS-dependent cell death accompanied by plasma membrane blistering, mitochondrial swelling, loss of mitochondrial membrane potential, and release of cytochrome c. Western blotting analysis showed that Met upregulated Bak expression but downregulated Bax expression. Most importantly, silencing Bak instead of Bax inhibited Met-induced loss of mitochondrial membrane potential, indicating the key role of Bak in Met-induced apoptosis. Live-cell fluorescence resonance energy transfer (FRET) analysis showed that Met unlocked the binding of Mcl-1 to Bak, and enhanced the binding of Bim to Bak and subsequent Bak homo-oligomerization. Western blotting analysis showed that Met enhanced AMPK phosphorylation and Bim expression, and compound C, an inhibitor of AMPK, inhibited Met-induced Bim upregulation. Although Met increased the expression of Bcl-xL, overexpression of Bcl-xL did not prevent Met-induced apoptosis. In summary, our data demonstrate for the first time that Met promotes ROS-dependent apoptosis by regulating the Mcl-1-Bim-Bak axis.
format	article
author	Hongce Chen Beini Sun Han Sun Lingjun Xu Guihao Wu Zhuang Tu Xuecheng Cheng Xuhong Fan Zihao Mai Qiling Tang Xiaoping Wang Tongsheng Chen
author_facet	Hongce Chen Beini Sun Han Sun Lingjun Xu Guihao Wu Zhuang Tu Xuecheng Cheng Xuhong Fan Zihao Mai Qiling Tang Xiaoping Wang Tongsheng Chen
author_sort	Hongce Chen
title	Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells
title_short	Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells
title_full	Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells
title_fullStr	Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells
title_full_unstemmed	Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells
title_sort	bak instead of bax plays a key role in metformin-induced apoptosis s in hct116 cells
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/ec5ff3f3032d4cd888f7caf48a7b9838
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Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells

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