The gut fermentation product butyrate, a chemopreventive agent, suppresses glutathione S-transferase theta (hGSTT1) and cell growth more in human colon adenoma (LT97) than tumor (HT29) cells
The gut fermentation product butyrate, a chemopreventive agent, suppresses glutathione S-transferase theta (hGSTT1) and cell growth more in human colon adenoma (LT97) than tumor (HT29) cells
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DOI：
10.1007/s00432-005-0013-4
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发表时间：
2005-10-01
影响因子：
3.6
通讯作者：
Pool-Zobel, BL
中科院分区：
文献类型：
--
作者：
Kautenburger, T;Beyer-Sehlmeyer, G;Pool-Zobel, BL
目的：丁酸膳食纤维肠道发酵产物抑制已建立的肿瘤细胞系HT29的生长。它还诱导属于谷胱甘肽S转移酶家族(GSTS)的解毒酶，即hGSTM2、hGSTP1、hGSTA4，而不是hGSTT1。在这里，我们研究了HT29的作用动力学，并与癌前病变LT97结肠腺瘤细胞进行了敏感性比较，以评估在细胞转化的两个阶段进行结肠癌化学预防的机制。方法：采用DNA定量、Northern/Western印迹或生化分析等方法检测丁酸对细胞生长的影响，通过测定细胞培养上清液中丁酸的残留浓度来测定丁酸的消耗量。结果：LT97腺瘤细胞对丁酸的摄取量是HT29细胞的2倍，对生长抑制的敏感性较HT29细胞高1.9 mM和4.0 mM。丁酸盐不能诱导LT97和HT29的GSTs，反而降低了hGSTT1。结论：丁酸盐通过抑制hGSTT1和细胞生长两种生存因子对人结肠癌细胞具有抑制作用，其中LT97比HT29更敏感。这些发现表明，丁酸在人类肠腔中的形成可能通过减少转化的结肠细胞的存活率而起到保护作用。
Purpose: The gut fermentation product of dietary fiber, butyrate, inhibits growth of HT29, an established tumor cell line. It also induces detoxifying enzymes belonging to the glutathione S-transferase family (GSTs), namely hGSTM2, hGSTP1, hGSTA4, but not of hGSTT1 . Here we investigated kinetics of effects in HT29 and compared sensitivities with preneoplastic LT97 colon adenoma cells, to assess mechanisms of colon cancer chemoprevention in two stages of cell transformation. Methods: We determined cell growth after butyrate treatment by quantifying DNA, GST expression by Northern/Western Blotting or biochemical analysis and butyrate consumption by measuring the residual concentrations in the cell culture supernatants. Stability of GST-theta (hGSTT1) mRNA was assessed in HT29 cells after inhibition of transcription with actinomycin D. Results: LT97 adenoma cells consumed twofold more butyrate and were more sensitive to growth inhibition than HT29 (EC(50)1.9 mM and 4.0 mM, respectively). Butyrate did not induce GSTs, but instead reduced hGSTT1 in LT97 and HT29. Conclusions: Butyrate has suppressing-agent activities in human colon cells by inhibiting two survival factors, namely hGSTT1 and cell growth, with LT97 more sensitive than HT29. These findings indicate that butyrate formation in the gut lumen of humans could be protective by reducing survival of transformed colon cells.