Molecular basis of cell migration inhibition by the dietary phytochemical piperine

Abstract

Metastasis, the migration of cells from a primary tumour site to distant tissues, is associated with the degradation of the epithelial basement membrane and extracellular matrix in connective tissue and often leads to poor prognosis in breast cancer. Matrix metalloproteinases (MMPs) are enzymes that are implicated in the destruction of the extracellular matrix and are overexpressed in breast cancer cells. Naturally occurring plant compounds known as phytochemicals are being investigated as possible anti-cancer agents. Piperine, a major alkaloid component of black pepper, is one such phytochemical that has shown chemotherapeutic effects in early experiments on human and mouse tumour cells. The current study investigates the potential of piperine to prevent cancer metastasis. The overall effect of piperine on MB-MDA-231 breast cancer cell migration was examined using a cell migration (wound-healing) assay. A mechanism of drug action was then explored by determining the effect of piperine on the mRNA transcription, production and activation of the gelatinases, MMP-2 and MMP-9, as well as the stromelysin, MMP-3. The cell migration assay showed that piperine significantly inhibited cancer cell migration at concentrations of 50 [mu]M. RT-qPCR analysis also showed that piperine significantly inhibited MMP-2 and MMP-9 mRNA expression after 48 hours of treatment. Preliminary results from western blot and gelatin zymography analyses indicated that piperine may also inhibit the translation and activity of MMP-2 and MMP-9. Piperine did not appear to affect MMP-3. These results offer further insight into the anti-metastatic action of piperine and suggest a possible novel treatment for aggressive breast cancers.