Berberine Activates Autophagy to Induce Apoptosis of Colorectal Cancer Cells in A Caspase-Dependent Manner

  OBJECTIVE  To investigate the potential mechanism of berberine in autophagy-mediated apoptosis of colorectal cancer.

  METHODS  HCT116 cells and a mouse model of xenograft tumor were used to detect the tumor suppressor effect of berberine and its potential mechanism. CCK8 assay was used to investigate the cell viability. Cell cloning assay was used to detect the effect of berberine on cell growth, and the influence of berberine on cell apoptosis was evaluated by using flow cytometry assay and TUNEL staining. The transmission electron microscope and mCherry-GFP-LC3B adenovirus translocation assays were used to observe the change of autophagy in cells. HE, immunohistochemical and TUNEL staining of mouse tissue were used to estimate the effect of berberine on colorectal cancer in vivo.

  RESULTS  Berberine inhibited the viability of tumor cells, and increased the apoptosis rate and LC3B level in HCT116 cells. 3-MA, CQ or BafA1 promoted the growth of HCT116 cells and cancelled the effect of berberine on apoptosis. Rapamycin increased the effect of berberine on up-regulating LC3B level in HCT116 cells, while Z-VAD-FMK or ATG5 siRNA abolished the effect of berberine on inducing cancer cells apoptosis. In vivo, berberine reduced tumor volume and tumor weight, and caused apoptosis in tumor tissues. In mouse tumor tissues, p-mTOR expression was significantly inhibited by berberine, while ATG5, ATG7, cleaved-caspase3 and cleaved-caspase8 were significantly up-regulated.

  CONCLUSION  Berberine induces autophagy and promotes caspase-dependent apoptosis of HCT116 cells, thereby inhibiting cell proliferation of colorectal cancer.