EFFECTS OF SHORT-CHAIN FATTY-ACIDS ON GROWTH AND DIFFERENTIATION OF THE HUMAN COLON-CANCER CELL-LINE HT29

EFFECTS OF SHORT-CHAIN FATTY-ACIDS ON GROWTH AND DIFFERENTIATION OF THE HUMAN COLON-CANCER CELL-LINE HT29
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DOI:
10.1002/ijc.2910520222
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发表时间:
1992-09-09
影响因子:
6.4
通讯作者:
MURAT, JC
MURAT, JC
中科院分区:
医学1区
文献类型:
--
作者:
GAMET, L;DAVIAUD, D;MURAT, JC

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短链脂肪酸(SCFAs),即丁酸盐、醋酸盐和丙酸盐,源于膳食纤维的细菌发酵,是大肠中主要的阴离子。本研究旨在探讨短链脂肪酸对人腺癌细胞HT29生长的影响。结果表明,在我们的培养条件下,丙酸盐和丁酸盐对HT29细胞的生长均有抑制作用,而乙酸盐对HT29细胞的生长无显著影响。丙酸盐或丁酸盐的抗增殖作用与抑制fcs诱导的鸟氨酸脱羧酶(ODC)的激活有关,ODC是多胺代谢的关键酶。丙酸盐或丁酸盐诱导的生长抑制不会被腐胺的加入逆转,这表明这些scfa并不仅仅作用于ODC/多胺系统。我们的数据显示,与乙酸不同,丙酸盐和丁酸盐诱导碱性磷酸酶活性增加,这反映了比未经处理的对照细胞更分化的表型。综上所述,我们的研究结果表明丙酸盐,像丁酸盐一样,可能在结肠生理中发挥重要作用,并可能部分解释膳食纤维对结肠癌发生的保护作用。
Short-chain fatty acids (SCFAs), namely butyrate, acetate and propionate, originate from the bacterial fermentation of dietary fibers and are the predominant anions present in the large bowel. Our study was carried out to investigate the effects of SCFAs on growth of the human adenocarcinoma cell line, HT29. The results show that, under our culture conditions, both propionate and butyrate inhibit growth of HT29 cells, whereas acetate has no significant effect. The antiproliferative effect of propionate or butyrate is associated with an inhibition of FCS-induced activation of ornithine decarboxylase (ODC), a key enzyme of polyamine metabolism. Inhibition of growth induced by either propionate or butyrate is not reversed by the addition of putrescine, which reveals that these SCFAs are not acting solely on the ODC/polyamine system. Our data show that propionate and butyrate, unlike acetate, induce an increase in alkaline phosphatase activity, which reflects a more differentiated phenotype than that of untreated control cells. Taken together, our results suggest that propionate, like butyrate, may play an important role in the physiology of the colon and could partially account for the protective effect of dietary fibers with respect to colon carcinogenesis.