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无胡椒碱的胡椒提取物对N-亚硝基甲基脲诱导的大鼠乳腺肿瘤发生的抗癌及防癌作用

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

作者信息

Sriwiriyajan Somchai, Tedasen Aman, Lailerd Narissara, Boonyaphiphat Pleumjit, Nitiruangjarat Anupong, Deng Yan, Graidist Potchanapond

机构信息

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.

Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.

出版信息

Cancer Prev Res (Phila). 2016 Jan;9(1):74-82. doi: 10.1158/1940-6207.CAPR-15-0127. Epub 2015 Oct 28.

DOI:10.1158/1940-6207.CAPR-15-0127
PMID:26511488
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 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.

摘要

黑胡椒常用于传统医学。本研究旨在调查一种不含胡椒碱的黑胡椒提取物(PFPE)对乳腺癌细胞以及对N-亚硝基甲基脲(NMU)诱导的大鼠乳腺肿瘤发生的抗癌和防癌活性。分别使用MTT法和蛋白质印迹分析在乳腺癌细胞中研究其细胞毒性作用及作用机制。根据经济合作与发展组织的指南进行急性毒性研究。将患有NMU诱导乳腺肿瘤的雌性斯普拉格-道利大鼠用于预防和抗癌研究。结果表明,PFPE通过诱导凋亡对管腔样乳腺癌细胞生长的抑制作用比对基底样细胞更强。此外,PFPE对乳腺癌细胞的选择性高于结肠直肠癌、肺癌和神经母细胞瘤细胞。在急性毒性研究中,以5000mg/kg体重的剂量单次口服PFPE,在14天观察期内未导致死亡和发病。在防癌研究中,用PFPE处理的大鼠中荷瘤大鼠的发生率为10%至20%。在抗癌活性研究中,与对照组和赋形剂组相比,PFPE处理组肿瘤的生长速度要慢得多。与对照组和赋形剂组相比,提取物本身未引起生化和血液学参数的变化。总之,PFPE对大鼠乳腺肿瘤发生具有低毒性和强大的抗肿瘤作用。

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