2. Academic Validation
  3. Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells

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

  • Cell Death Discov. 2021 Nov 22;7(1):363. doi: 10.1038/s41420-021-00755-y.
Hongce Chen 1,  Beini Sun 1,  Han Sun 1,  Lingjun Xu 2,  Guihao Wu 2,  Zhuang Tu 1,  Xuecheng Cheng 1,  Xuhong Fan 2,  Zihao Mai 1,  Qiling Tang 1,  Xiaoping Wang 3,  Tongsheng Chen 4 5
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, 510631, Guangzhou, China.
  • 2 Department of Pain Management, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, China.
  • 3 Department of Pain Management, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, China. txp2938@jnu.edu.cn.
  • 4 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, 510631, Guangzhou, China. chentsh@scnu.edu.cn.
  • 5 SCNU Qingyuan Institute of Science and Technology Innovation Co., Ltd., South China Normal University, 511500, Qingyuan, China. chentsh@scnu.edu.cn.
PMID: 34811352 DOI: 10.1038/s41420-021-00755-y
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z