学术报告 5

Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries.

黑覆盆子提取物和组分抑制癌前病变和恶性人口腔细胞 系的生长。

原文链接官方网址：https://www.ncbi.nlm.nih.gov/pubmed

Nutr Cancer. 2005;51(2):207-17.

营养癌症。2005; 51（2）：207-17。

Han C1, Ding H, Casto B, Stoner GD, D'Ambrosio SM.

Author information

Department of Radiology, The Ohio State University, Columbus 43210, USA.

作者信息

俄亥俄州立大学放射学系，哥伦布 43210，美国。

Abstract

Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory

 reside in specific components that target aberrant signaling pathways regulating cell cycle progression.

黑覆盆子是化学预防性植物化学物质的丰富天然来源。最近的研究表明冻干的黑覆盆子能够抑制 啮齿类动物的口腔，食管和结肠癌的发展，黑覆盆子的提取物抑制苯并（a）芘诱导的仓鼠胚胎 成纤维细胞的细胞转化。然而，黑覆盆子化学预防的分子机制和活性成分尚不清楚。在这项研究 中，我们发现黑色树莓，阿魏酸和 β-谷甾醇的 2 种主要化学预防成分和用乙醇（RO-ET）在冷 冻干燥黑覆盆子的有机提取物的硅胶柱色谱法中洗脱的部分抑制生长的恶化前和恶性但不是正 常人口腔上皮细胞系。另一部分用 CH 2 Cl 2 /乙醇（DM：ET）和鞣花酸抑制正常以及恶化前 和恶性人口腔细胞系的生长。我们调查了阿魏酸和 β-谷甾醇和 RO-ET 部分使用流式细胞术和细 胞周期调节蛋白的 Western 印迹选择性抑制恶化前和恶化口腔细胞的生长的分子机制。用RO-ET 级分处理细胞后细胞周期分布没有可辨别的变化。在与阿魏酸温育后，癌前和恶性细胞 重新分布到细胞周期的 G2 / M 期。β-谷甾醇处理的癌前期和恶性细胞分别在 G0 / G1 期和 G2/ M 期累积。RO-ET 分数降低癌前期细胞中细胞周期蛋白 A 和细胞分裂周期基因 2（cdc2）的 水平，细胞周期蛋白 B1，细胞周期蛋白 D1，和 cdc2 在恶性细胞系中。该部分也升高恶性细胞 系中 p21waf1 / cip1 的水平。阿魏酸处理导致两种细胞系中细胞周期蛋白 B1 和 cdc2 水平增 加，并且在恶性细胞系中诱导 p21waf1 / cip1。β-谷甾醇降低细胞周期蛋白 B1 和 cdc2 的水平， 同时增加恶化前和恶化细胞系中的 p21waf1 / cip1。这些结果首次表明黑覆盆子对恶化前和恶 性人口腔细胞的生长抑制作用可能存在于靶向调节细胞周期进程的异常信号通路的特定组分中。 阿魏酸处理导致两种细胞系中细胞周期蛋白 B1 和 cdc2 水平增加，并且在恶性细胞系中诱导 p21waf1 / cip1。β-谷甾醇降低细胞周期蛋白 B1 和 cdc2 的水平，同时增加恶化前和恶化细胞 系中的 p21waf1 / cip1。这些结果首次表明黑覆盆子对恶化前和恶性人口腔细胞的生长抑制作中细胞周期蛋白 B1 和 cdc2 水平增加，并且在恶性细胞系中诱导 p21waf1 / cip1。β-谷甾醇降低细胞周期蛋白 B1 和 cdc2 的水平，同时增加恶化前和恶化细胞系中的 p21waf1 / cip1。这些 结果首次表明黑覆盆子对恶化前和恶性人口腔细胞的生长抑制作用可能存在于靶向调节细胞周 期进程的异常信号通路的特定组分中。

PMID:15860443                  

DOI:10.1207/s15327914nc5102_11

源自：

美国国家医学图书馆

美国国家卫生研究院

US National Library of Medicine/

Us National Institutes of Health/