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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.

Bacillus coagulans has a potential role in improving intestinal injury. However, the specific mechanism is still unclear. In this study, the protective effect of B. coagulans MZY531 on intestinal mucosa injury in cyclophosphamide (CYP)-induced immunosuppressed mice were investigated. The results indicated that the immune organ (thymus and spleen) indices of B. coagulans MZY531 treatment groups were significantly increased compared to the CYP group. B. coagulans MZY531 administration promotes the expression of immune proteins (IgA, IgE, IgG, and IgM). B. coagulans MZY531 could upregulate the ileum levels of IFN-γ, IL-2, IL-4, and IL-10 in immunosuppressed mice. Moreover, B. coagulans MZY531 restores the villus height and crypt depth of the jejunum and alleviates injury of intestinal endothelial cells caused by CYP. Furthermore, the western blotting results showed that B. coagulans MZY531 ameliorated CYP-induced intestinal mucosal injury and inflammatory via up-regulates the ZO-1 pathway and down-regulates the expression of the TLR4/MyD88/NF-κB pathway. After treatment with B. coagulans MZY531, the relative abundance of Firmicutes phylum was dramatically increased, as well as the genera of Prevotella and Bifidobacterium, and reducing harmful bacteria. These findings suggested that B. coagulans MZY531 has a potential immunomodulatory activity on chemotherapy-induced immunosuppression.

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