APOPTOSIS IN COLORECTAL TUMOR-CELLS - INDUCTION BY THE SHORT-CHAIN FATTY-ACIDS BUTYRATE, PROPIONATE AND ACETATE AND BY THE BILE-SALT DEOXYCHOLATE
APOPTOSIS IN COLORECTAL TUMOR-CELLS - INDUCTION BY THE SHORT-CHAIN FATTY-ACIDS BUTYRATE, PROPIONATE AND ACETATE AND BY THE BILE-SALT DEOXYCHOLATE
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DOI：
10.1002/ijc.2910600322
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发表时间：
1995-01-27
影响因子：
6.4
通讯作者：
PARASKEVA, C
中科院分区：
文献类型：
--
作者：
HAGUE, A;ELDER, DJE;PARASKEVA, C
膳食纤维经结肠菌发酵产生短链脂肪酸乙酸、丙酸和丁酸。我们之前已经证明丁酸钠可诱导3种结直肠癌细胞系的细胞凋亡。我们将研究扩展到3个腺瘤和4个癌细胞系，研究丙酸盐和醋酸盐是否也能诱导细胞凋亡。3种短链脂肪酸在生理浓度下均可诱导细胞凋亡，但以丁酸盐效果最好。由于这些脂肪酸是由膳食纤维的细菌发酵产生的，这可能在一定程度上解释了高纤维饮食与低结直肠癌发病率之间的相关性。丁酸钠诱导7种细胞系凋亡；然而，4个癌细胞系中有2个（PC/JW/FI和S/KS/FI）对丁酸盐诱导的细胞凋亡的抗性比3个腺瘤细胞系更强，这表明至少一些癌可能进化出保护细胞免受诱导凋亡的机制。此前有报道称胆汁酸脱氧胆酸可能是大肠肿瘤的促进剂，膳食纤维可降低其水平。10 nM ~ 0.1 mM的浓度对体外培养的结肠癌细胞增殖和凋亡均无影响。而在0.5 mM的浓度下，对细胞凋亡有明显的诱导作用。这些结果可能对结直肠癌的病因学有一定的意义。(C) 1995 Wiley-Liss, Inc。
The short chain fatty acids acetate, propionate and butyrate are produced when dietary fibre is fermented by the colonic bacteria. We have previously shown that sodium butyrate induces apoptosis in 3 colorectal tumour cell lines. We have extended our study to 3 adenoma and 4 carcinoma cell lines and investigated whether propionate and acetate also induce apoptosis. All 3 short chain fatty acids induced apoptosis at physiological concentrations, but of the 3, butyrate was the most effective. Since these fatty acids are produced as a result of bacterial fermentation of dietary fibre, this may in part explain the correlation between a high-fibre diet and low colorectal cancer incidence. Sodium butyrate induced apoptosis in all 7 of the cell lines studied; however, 2 of the 4 carcinoma cell lines (PC/JW/FI and S/KS/FI) were more resistant to butyrate-induced apoptosis than the 3 adenoma cell lines, suggesting that at least some carcinomas may evolve mechanisms to protect the cells from the induction of apoptosis. The bile acid deoxycholic acid has previously been reported as a possible tumour promoter in the large intestine and its levels are reduced by dietary fibre. Concentrations of between 10 nM and 0.1 mM had no effect on either the proliferation or apoptosis of colonic tumour cells in vitro. However, a significant induction of apoptosis was obtained at a concentration of 0.5 mM. These results may have significance for the aetiology of colorectal cancer. (C) 1995 Wiley-Liss, Inc.