Effect of Piper nigrum Ethanolic Extract on Human Breast Cancer Cell Growth and Cell Migration

Background: Piper nigrum (PN) is widely used as a traditional medicine, which has anti-cancer activity among others. Objective: Our study purposes to illuminate the inhibition of PN effects on breast cancer cells growth and migration along with its mechanisms. Materials and Methods: The piperine in the young fruit of PN extract was determined by the high-performance liquid chromatography method. Growth inhibition with a mechanism of PN extract was studied in the MCF-7 cells using sulforhodamine B assay, cell cycle analysis, colony formation, caspase-3 activity, and reactive oxygen species formation. Furthermore, the anti-migratory effects of PN were investigated using wound healing, matrigel migration, and gelatin zymography assay. Finally, PN mechanism was determined by reverse transcription polymerase chain reaction and Western blotting for the gene and protein levels. Results: Piperine level was showed at a high concentration in the PN extract. Further, the PN extract suppressed Rac1 mRNA expression in the mevalonate (MVA) pathway as well as repressed Rac1 and RhoA protein expression. Interestingly, PN stimulated growth inhibition in dose- and time-dependent as well as being accompanied by increasing the G1 phase arrest and inhibiting cyclin D1 and NF-kappa B as well as inducing caspase-3 expression. The PN extract inhibited MCF-7 cell migration by reducing matrix metalloproteinases (MMP) 9 protein expression as well as MMP 2, MMP 9, VEGFA, and ICAMP1 gene expression. Conclusion: PN could be herbal medicine for anti-cancer and anti-migratory activities with a correlation to the MVA pathway; therefore, PN maybe deserving further to study as a new candidate for treating breast cancer.