Berberine suppresses the migration and invasion of colon cancer cells by inhibition of lipogenesis through modulation of promyelocytic leukemia zinc finger-mediated sterol-regulatory element binding proteins cleavage-activating protein ubiquitination

Objectives: This study was aimed to explore whether and how berberine suppresses colon Cancer cell metastasis via lipid modulation.

Methods: Lipid accumulation was measured by an oil red O staining kit. The expression of proteins and message RNA was detected by Western blot and quantitative Real-Time PCR. The interaction of sterol-regulatory element-binding proteins cleavage-activating protein (SCAP) with promyelocytic leukaemia zinc finger (PLZF) was confirmed by co-immunoprecipitation assay. Expressions of fatty acid synthase (FASN) and PLZF were knocked down by specific small interfering RNA.

Key findings: Berberine inhibited the migration and invasion of HCT-8, HCT-116 and HT-29 cells. Moreover, it was observed that berberine decreased lipid droplet accumulation. FASN knockdown abolished the inhibitory effects of berberine on cell migration and invasion. Further investigation revealed that berberine induced the ubiquitination degradation of SCAP. And PLZF interacted with SCAP and promoted its ubiquitination, which was inhibited by berberine treatment. Silence of PLZF impaired the effects of berberine on SCAP ubiquitination and lipogenesis.

Conclusions: Berberine suppressed lipogenesis via promotion of PLZF-mediated SCAP ubiquitination, thereby inhibiting colon Cancer cell metastasis.