Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats.
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 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% 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.
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand. Department of Pharmacology, Faculty of Science, Prince of Songkla University, Songkhla, Thailand.
Somchai
S
Sriwiriyajan
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Aman
A
Tedasen
Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Narissara
N
Lailerd
Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Pleumjit
P
Boonyaphiphat
Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Anupong
A
Nitiruangjarat
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Yan
Y
Deng
Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand. The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Songkhla, Thailand. gpotchan@medicine.psu.ac.th.
Potchanapond
P
Graidist
D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry*; D017209:Apoptosis; D052117:Benzodioxoles / Q000737:chemistry*; D001835:Body Weight; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D051379:Mice; D008813:Mice, Inbred ICR; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D010936:Plant Extracts / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D016588:Anticarcinogenic Agents; D052117:Benzodioxoles; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D008770:Methylnitrosourea; C008922:piperine