Kobayashi Hanako, Tan Er Mei, Fleming Sharon E
Department of Nutritional Science and Toxicology, University of California, Berkeley, CA 94720, USA.
Nutr Cancer. 2003;46(2):202-11. doi: 10.1207/S15327914NC4602_14.
Butyric acid, one of the short-chain fatty acids produced by microbial fermentation in the colon, exhibits antiproliferative activities in various cancer cell lines. The initial objective of the study was to assess whether the effect of sodium butyrate (NaB) on cell growth differed by p53 status of the cells. Four human colorectal adenocarcinoma cell lines were used: HT29 (p53 point mutation), Caco2 (p53 truncation), LS513 (p53 wild type), and Lovo (p53 wild type). NaB significantly inhibited cell growth in all four cell lines. NaB arrested HT29 and LS513 cells in G0/G1 and Caco2 and Lovo in G2-phase. A second objective was to determine whether NaB similarly affected the cyclin-dependent kinase inhibitor, p21WAF1/CIP1. In all cell lines, p21 mRNA levels were immediately elevated after NaB exposure, and p21 protein levels were increased within 6 h. NaB increased p21 promoter activity in both Caco2 and Lovo, suggesting p53 independence. NaB did not influence p21 mRNA stability. Although three DNase I hypersensitivity sites were identified in the region of the p21 gene, induction of p21 mRNA by NaB was not accompanied by relaxation of the chromatin in the region of the p21 gene.
丁酸是结肠中微生物发酵产生的短链脂肪酸之一，在多种癌细胞系中表现出抗增殖活性。该研究的最初目的是评估丁酸钠（NaB）对细胞生长的影响是否因细胞的p53状态而异。使用了四种人类结肠腺癌细胞系：HT29（p53点突变）、Caco2（p53截短）、LS513（p53野生型）和Lovo（p53野生型）。NaB显著抑制了所有四种细胞系的细胞生长。NaB使HT29和LS513细胞停滞在G0/G1期，使Caco2和Lovo细胞停滞在G2期。第二个目的是确定NaB是否同样影响细胞周期蛋白依赖性激酶抑制剂p21WAF1/CIP1。在所有细胞系中，NaB暴露后p21 mRNA水平立即升高，p21蛋白水平在6小时内增加。NaB增加了Caco2和Lovo中p21启动子的活性，表明其不依赖于p53。NaB不影响p21 mRNA的稳定性。尽管在p21基因区域鉴定出三个DNase I超敏位点，但NaB诱导p21 mRNA的表达并未伴随着p21基因区域染色质的松弛。
