Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines.
Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines.
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发表时间：
1994-06
期刊：
影响因子：
11.2
通讯作者：
B. Heerdt;M. Houston;L. Augenlicht
中科院分区：
文献类型：
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作者：
B. Heerdt;M. Houston;L. Augenlicht
正常结肠粘膜的结构表明，接近隐窝顶部的终末分化上皮细胞被挤出到结肠腔内。形态学研究已经在隐窝-管腔界面附近的分化表型中发现了凋亡细胞，这表明分化、凋亡和细胞脱落的途径之间存在联系。我们在HT29和SW620细胞中研究了这些过程，发现与贴壁细胞相比，在标准的、未诱导的培养条件下脱落的细胞表现出非随机DNA片段化的凋亡特征。此外，这些积聚在培养液中的凋亡细胞表现出更多的分化表型。由于短链脂肪酸(SCFA)是体内结肠细胞分化的天然效应物质，我们研究了三种4碳原子的SCFA在这些结肠癌细胞系中促进分化和凋亡的特异性，从而促进了条件培养液中脱落细胞的聚集。然而，未支化的SCFA丁酸诱导了更多的分化表型并促进了细胞的凋亡，而丁酸的两个衍生物支化异丁酸和不可代谢的氟取代类似物七氟丁酸在诱导分化或凋亡方面都无效。因此，促进结肠癌细胞的分化和凋亡与SCFA的结构和最有可能的利用有关。
The architecture of normal colonic mucosa suggest that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.