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

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-3 beta 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-3 beta, and p-GSK-3 beta. 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-3 beta 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-3 beta proteins. In summary, our in vitro and in vivo analyses show that curcumin downregulates BCLAF1 expression, inhibits the activation of the PI3K/AKT/GSK-3 beta pathway, and triggers mitochondrial apoptosis in HCC. These findings un-cover a potential therapeutic strategy leveraging the antitumor effects of curcumin against HCC.

Automated summary

The study demonstrated that curcumin triggers mitochondrial apoptosis in HCC by inhibiting the PI3K/AKT/GSK-3 beta signaling pathway and downregulating BCLAF1 expression, thereby inhibiting tumor growth. This highlights a potential therapeutic strategy leveraging the antitumor effects of curcumin against HCC.