Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated
the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells.
Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells,
without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage
of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression
was decreased and p21Waf1/Cip1 expression was increased in piperine-treated TNBC cells. Piperine also inhibited
survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the
mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic
for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was
impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an
antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth
of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may
be useful in the treatment of TNBC.