Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats

Abstract

Piper nigrum (P. nigrum) is commonly used in traditional medicine. This current study aimed to investigate the anticancer and cancer preventive activity of a piperine-free P. 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 the Organization for Economic Co-operation and Development guideline. Female Sprague-Dawley rats with NMU-induced mammary tumors were used in preventive and anticancer studies. The results showed that PFPE inhibited the growth of luminal-like breast cancer cells more so than the basallike 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% to 20% in rats treated with PFPE. For the anticancer activity study, the growth rate of tumors in the presence of PFPE-treated groups was much slower when compared with the control and vehicle groups. The extract itself caused no changes to the biochemical and hematologic parameters when compared with the control and vehicle groups. In conclusion, PFPE had a low toxicity and a potent antitumor effect on mammary tumorigenesis in rats.Cancer Prev Res; 9(1); 74-82. Ó2015 AACR.

A systematic review on ethnomedicines of anti-cancer plants

“…According to Damanhouri and Ahmed (Damanhouri and Ahmad, ) piperine is non‐genotoxic. Sriwiriyajan et al () checked toxicity of piperine free Piper nigrum extract at the dose of 5000 mg/kg but resulted in non‐morbidity and non‐mortality showing no toxic effect on mammary tumorigenesis in rats. In another study, aqueous extract of Plantago major administred orally at the regular dose of 2000 mg/kg for 40 days did not result in mortality (Garcia et al ., ).…”

Quality variation and standardization of black pepper (Piper nigrum): A comparative geographical evaluation based on instrumental and metabolomics analysis

“…However, there may be many other chemical compounds in the plant that may play the same role. In this regard, Sriwiriyajan et al () performed a study using PPN‐free P. nigrum (PFPN) in which potent antitumor activity with low toxicity was observed for PFPN (Sriwiriyajan et al, ). Thus, it is vital to isolate, elucidate the proper structure, and explore the mechanism of action for all chemicals present in a plant, irrespective of the main or major active principle (i.e.…”

Naturally occurring Piper plant amides potential in agricultural and pharmaceutical industries: perspectives of piperine and piperlongumine

“…Further study is needed to explore how to combine piperine with other natural materials to treat cancer cells that have developed resistance to conventional anticancer drugs. Interestingly, piperine-free P. nigrum extracts were prepared to study their effects on N-nitrosomethylurea-induced mammary tumorigenesis in rats [36]. Recently, a review paper was published that collected results from several studies on the anticancer effects of piperine towards cancerous and normal cells [37].…”