Cancer metastasis is the primary cause of
cancer morbidity and mortality. Anti-
metastasis mechanism of
skin cancer by 13-butoxyberberine
bromide, a novel
berberine derivative, has not yet been reported. This study investigated the effects of 13-butoxyberberine
bromide on migration and invasion of
skin cancer A431 cells. The cytotoxicity of 13-butoxyberberine
bromide was determined by MTT assay. The effect of 13-butoxyberberine
bromide on cell migration and invasion were examined using a wound-healing assay, transwell migration assay, and transwell invasion assay, respectively. The cell adhesion ability was determined by an adhesion assay.
Protein expressions that play important roles in
cancer migration and invasion were evaluated by Western blot analysis. The results showed that 13-butoxyberberine
bromide effectively inhibited cell migration, invasion, and adhesion in A431 cells. Interestingly, 13-butoxyberberine
bromide was more effective for cell migration inhibition than
berberine. In addition, 13-butoxyberberine
bromide showed anti-migration and anti-invasion effects by down-regulated MMP-2 and MMP-9 expression and up-regulated
TIMP-1 and
TIMP-2 expression in A431 cells. Moreover, pretreatment with 13-butoxyberberine
bromide significantly inhibited
EGF-induced cell migration and p-EGFR, ERK, p-ERK, STAT3, and p-STAT3 expressions in A431 cells at lower concentrations when compared with the
berberine. These findings indicated that 13-butoxyberberine
bromide could be further developed as an
anticancer agent.