Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function.
Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function.
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发表时间：
1997-05
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通讯作者：
B. Heerdt;M. Houston;L. Augenlicht
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作者：
B. Heerdt;M. Houston;L. Augenlicht
丁酸盐是纤维微生物发酵过程中产生的一种短链脂肪酸，可在体外诱导结肠上皮细胞的生长停滞、分化和凋亡，我们之前的工作表明这种诱导与线粒体活性密切相关。在这里，我们证明诱导 12 小时后，SW620 人结肠癌细胞在细胞周期的 G0-G1 和 G2-M 中同时积累。四小时后，在 G0-G1 到 G2-M 停滞期间，细胞开始凋亡。使用一系列不相关的调节线粒体功能的试剂，我们证明线粒体电子传递和膜电位对于丁酸盐介导的生长停滞和细胞凋亡的启动至关重要。结肠肿瘤发生的特征是增殖、凋亡和线粒体活性异常。因此，丁酸盐可以通过诱导增强线粒体功能的途径来降低结肠癌的风险，最终导致结肠上皮细胞生长停滞和凋亡。
Butyrate, a short-chain fatty acid produced during microbial fermentation of fiber, induces growth arrest, differentiation, and apoptosis of colonic epithelial cells in vitro, and our prior work has shown that this induction is tightly linked to mitochondrial activity. Here we demonstrate that 12 h following induction, SW620 human colonic carcinoma cells accumulate simultaneously in G0-G1 and G2-M of the cell cycle. Four h later, during this G0-G1 to G2-M arrest, cells begin to undergo apoptosis. Using a series of unrelated agents that modulate mitochondrial functions, we demonstrate that mitochondrial electron transport and membrane potential are critical in initiation of this butyrate-mediated growth arrest and apoptosis. Colonic tumorigenesis is characterized by abnormalities in proliferation, apoptosis, and mitochondrial activities. Thus, butyrate may reduce risk for colon cancer by inducing a pathway that enhances mitochondrial function, ultimately resulting in initiation of growth arrest and apoptosis of colonic epithelial cells.