In Vitro Inhibition of Piper nigrum and Piperine on Growth, Migration, and Invasion of PANC-1 Human Pancreatic Cancer Cells

Several dietary and medicinal herbs have been shown to be effective in the treatment and prevention of cancer. Although Piper nigrum has been shown to have anti-cancer activities against various cancer cells, its anti-pancreatic cancer properties have not been reported. In the present study, P. nigrum extract (PNE) inhibited proliferation of PANC-1 human pancreatic cancer cells. Flow cytometry showed G0/G1 arrest caused by PNE in PANC-1 cells. In addition, Western blot analysis showed that PNE suppressed the protein levels of cell cycle regulators such as cyclin B1, cyclin D1, survivin, and Forkhead box M1 (FoxM1). These findings suggested that the inhibitory activity of PNE against the growth of PANC-1 cells was correlated with cell cycle arrest and repression of cell cycle regulators. Wound healing and trans-well assays showed that PNE suppressed migration and invasion of PANC-1 cells. Piperine, a major alkaloid of Piper nigrum, was identified as the main component of PNE by HPLC analysis. Piperine also attenuated the cell growth, migration, and invasion of PANC-1 cells, suggesting its contribution to the anti-pancreatic cancer effects of PNE. These results demonstrate that PNE and its major constituent, piperine, have anti-pancreatic cancer properties such as growth-inhibition, anti-migration, and anti-invasion of cancer cells.