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  2. Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1-mediated modulation of PI3K/AKT/GSK-3β signaling

Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1-mediated modulation of PI3K/AKT/GSK-3β signaling

  • Life Sci. 2022 Oct 1;306:120804. doi: 10.1016/j.lfs.2022.120804.
Chunhua Bai 1 Jiaqi Zhao 2 Jielin Su 2 Jiaxin Chen 2 Xinmu Cui 2 Manqing Sun 2 Xuewu Zhang 3
Affiliations

Affiliations

  • 1 Yanbian University School of Medicine, Yanji 133000, China; Shenzhen Hyzen Hospital, Shenzhen 518000, China.
  • 2 Yanbian University School of Medicine, Yanji 133000, China.
  • 3 Yanbian University School of Medicine, Yanji 133000, China. Electronic address: zhangxuewu@ybu.edu.cn.
Abstract

Curcumin is a yellow pigment extracted from the rhizome of turmeric, a traditional Chinese medicine. Here, we tested the hypothesis that curcumin-mediated downregulation of BCLAF1 triggers mitochondrial Apoptosis in hepatoma cells by inhibiting PI3K/Akt/GSK-3β signaling. Treatment of the human hepatoma cell lines, HepG2 and SK-Hep-1, with various concentrations of curcumin revealed a time-dependent and concentration-dependent inhibition of cell proliferation, increased Apoptosis, cell cycle arrest at the G0/G1 phase, reduced mitochondrial membrane potential, and reduced expression levels of PI3K, p-PI3K, Akt, p-AKT, GSK-3β, and p-GSK-3β. Additionally, curcumin suppressed the levels of apoptotic factors after treating the cells with LY294002, a PI3K Inhibitor. Curcumin also suppressed the expression of BCLAF1. Treating stable BCLAF1 knockout HepG2 and SK-Hep-1 cells with curcumin further enhanced Apoptosis and increased the number of cells in G0/G1 cell cycle arrest, while inhibiting the downregulation of PI3K/Akt/GSK-3β pathway-related proteins. Treatment of a nude mouse xenograft model bearing HepG2 cells with curcumin inhibited tumor growth, disrupted the cellular structure of the tumor tissue, and suppressed the expression of BCLAF1 and PI3K/Akt/GSK-3β proteins. In summary, our in vitro and in vivo analyses show that curcumin downregulates BCLAF1 expression, inhibits the activation of the PI3K/Akt/GSK-3β pathway, and triggers mitochondrial Apoptosis in HCC. These findings uncover a potential therapeutic strategy leveraging the antitumor effects of curcumin against HCC.

Keywords

BCLAF1; Curcumin; Liver cancer; Mitochondrial apoptosis; PI3K/AKT/GSK-3β pathway.

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