Intake of dietary fiber may protect against colon cancer. The anticancer property is associated with an increased production of short chain fatty acids (SCFAs), including acetate, propionate and butyrate, during dietary fiber fermentation in the colon. However, the mechanisms remain to be determined. We hypothesized that butyrate exhibits a stronger inhibitory potential against colon cancer cell proliferation compared with acetate and propionate. We determined the half maximal inhibitory concentrations (IC50) of SCFAs in HCT116 human colon cancer cell proliferation by examining cell growth curves. At 24- and 48-hour time points, IC50 (mmol/L) concentrations of acetate, propionate, and butyrate were [66.0 and 29.0], [9.2 and 3.6], and [2.5 and 1.3], respectively. Consistent with the greater anti-proliferative effect, butyrate exhibits >3-fold stronger potential for inducing cell cycle arrest at the G2 phase with a drop in S-phase fraction (including c-Myc/p21 signaling) and apoptosis when compared with acetate and propionate. Subsequently, we focused on the effect of butyrate on apoptotic gene expression. Using a PCR array analysis, we identified 17 pro-apoptotic genes, 6 anti-apoptotic genes, and 4 cellular mediator genes with >1-fold increase or decrease in mRNA levels out of 93 apoptosis related genes in butyrate-treated HCT116 cells when compared with untreated HCT116 cells. These genes were mainly involved in the TNF, NFκB, CARD, and BCL-2 regulated pathways. Taken together, our data indicate a greater inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis.

中文翻译：

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丁酸盐通过细胞周期阻滞和细胞凋亡对人结肠癌细胞增殖的抑制作用优于丙酸盐和乙酸盐：将膳食纤维与癌症预防联系起来

摄入膳食纤维可以预防结肠癌。在结肠中的膳食纤维发酵过程中，抗癌特性与短链脂肪酸 (SCFA) 的产生增加有关，包括乙酸盐、丙酸盐和丁酸盐。然而，机制仍有待确定。我们假设与乙酸盐和丙酸盐相比，丁酸盐对结肠癌细胞增殖具有更强的抑制潜力。我们通过检查细胞生长曲线确定了 SCFAs 在 HCT116 人结肠癌细胞增殖中的半数最大抑制浓度 (IC50)。在 24 和 48 小时时间点，乙酸盐、丙酸盐和丁酸盐的 IC50 (mmol/L) 浓度分别为 [66.0 和 29.0]、[9.2 和 3.6] 和 [2.5 和 1.3]。与更强的抗增殖作用一致，丁酸盐表现出 > 与醋酸盐和丙酸盐相比，诱导细胞周期停滞在 G2 期的潜力高出 3 倍，同时 S 期分数（包括 c-Myc/p21 信号传导）和细胞凋亡减少。随后，我们专注于丁酸盐对凋亡基因表达的影响。使用 PCR 阵列分析，我们在丁酸盐处理的 HCT116 细胞中鉴定了 93 个凋亡相关基因中 17 个促凋亡基因、6 个抗凋亡基因和 4 个细胞介质基因，其 mRNA 水平增加或减少了 >1 倍未经处理的 HCT116 细胞。这些基因主要参与TNF、NFκB、CARD和BCL-2调控通路。总之，我们的数据表明丁酸盐通过细胞周期停滞和细胞凋亡对人结肠癌细胞增殖的抑制作用比丙酸盐和乙酸盐更强。