Anti-cancer and cancer preventive effects of a piperine free Piper nigrum extract on N-nitrosomethylurea induced mammary tumorigenesis in rats.
Cancer Prev Res (Phila). 2015 Oct 28. Epub 2015 Oct 28. PMID: 26511488
Piper nigrum is commonly used in traditional medicine. This current study aimed to investigate the anti-cancer and cancer preventive activity of a piperine free Piper nigrum extract (PFPE) against breast cancer cells and N-nitrosomethylurea (NMU)-induced mammary tumorigenesis in rats. The cytotoxic effects and the mechanism of action were investigated in breast cancer cells using the MTT assay and Western blot analysis, respectively. An acute toxicity study was conducted according to OECD guideline. Female Sprague-Dawley rats with NMU-induced mammary tumors were used in preventive and anti-cancer studies. The results showed that PFPE inhibited the growth of luminal-like breast cancer cells more so than the basal-like ones by induction of apoptosis. In addition, PFPE exhibited greater selectivity against breast cancer cells than colorectal cancer, lung cancer, and neuroblastoma cells. In an acute toxicity study, a single oral administration of PFPE at a dose of 5,000 mg/kg body weight resulted in no mortality and morbidity during a 14-day observation period. For the cancer preventive study, the incidence of tumor bearing rats was 10-20% in rats treated with PFPE. For the anti-cancer activity study, the growth rate of tumors in the presence of PFPE treated groups was much slower when compared to the control and vehicle groups. The extract itself caused no changes to the biochemical and hematological parameters when compared to the control and vehicle groups. In conclusion, PFPE had a low toxicity and a potent anti-tumor effect on mammary tumorigenesis in rats.