Anti-cancer effects of Piper nigrum via inducing multiple molecular signaling in vivo and in vitro.
J Ethnopharmacol. 2016 May 4. Epub 2016 May 4. PMID: 27155135
ETHNOPHARMACOLOGICAL RELEVANCE: Piper nigrum is widely used as a folk medicine including usage for pain relief, fevers, as well as an anti-cancer agent. However the crude extracts of piperine free P. nigrum (PFPE), which inhibits breast cancer, and its mechanisms are still being kept secret. This research is aimed to elucidate the anti-cancer effects of PFPE and its mechanisms.
MATERIALS AND METHODS: Anti-cancer effects of PFPE were investigated in N-nitroso-N-methylurea (NMU)-induced mammary tumorigenesis rats and breast cancer cell lines MCF-7 and ZR-75-1. Furthermore, the cancer prevention effects of PFPE were investigated in rats. Western blotting was employed to study proteins levels induced by PFPE.
RESULTS: PFPE was found to up-regulate p53, and down-regulate estrogen receptor (ER), E-cadherin (E-cad), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), c-Myc, and vascular endothelial growth factor (VEGF) levels in breast cancer rats. Moreover, PFPE decreased protein levels of E-cad, c-Myc, and VEGF in MCF-7 cells. These results suggest that PFPE can enhance breast cancer cell response to phytochemicals, then induce cell cycle arrest, and inhibit cancer cell proliferation resulting in tumor size decrease in the PFPE treated group. It is further suggests that PFPE may suppress tumor cell invasion, migration, and angiogenesis. In addition, PFPE possessed cancer prevention effects through generation reactive oxygen species (ROS) to higher cancer cell cellular stress.
CONCLUSIONS: PFPE could possess the anti-cancer and cancer prevention effect; hence, it deserves further investigation as a novel candidate for treating breast cancer.