Reese D H, Gratzner H G, Block N L, Politano V A
Cancer Res. 1985 May;45(5):2308-13.
The actions of butyrate and related short-chain fatty acids were analyzed on the 9-1C retinoid-responsive rat prostatic adenocarcinoma cell. The 9-1C cells, which are inducible for alkaline phosphatase (AP) by retinoic acid, were also inducible for the enzyme by three- to six-carbon fatty acids. The most effective inducer was the four-carbon acid, butyrate, which caused an essentially linear increase in AP activity in the concentration range of 2 to 10 mM. A comparison of AP induction by butyrate and retinoic acid showed the retinoid to be a more potent inducer of the enzyme by several orders of magnitude. Butyrate and related short-chain fatty acids also suppressed 9-1C cell growth, an effect which is not mediated by retinoic acid in these cells. Total growth suppression was achieved at butyrate concentrations of 5 mM and above; 1.5 mM caused 50% inhibition. As in the case of AP induction, all three- to six-carbon fatty acids suppressed growth to some extent, although butyrate was the most effective. The order of carbon chain length effectiveness for both AP induction and growth suppression by the fatty acids was 4 greater than 5 greater than 3 greater than 6. Butyrate appeared to be unique among the various fatty acids in causing an increase in cell protein. The protein content of 9-1C cells cultured in the presence of 4 mM butyrate for 72 h was more than 4-fold greater than that of control cells. This observation paralleled observations on cell volumes analyzed by forward-angle light-scatter flow cytometry, which showed a concentration-related increase in the cross-sectional areas of 9-1C cells following butyrate treatment. This effect has also been shown, in a recent study, to be mediated by retinoids. One of the most striking effects of butyrate treatment was on cellular morphology. The fatty acid caused 9-1C cells, which normally grow in a disorganized array with no apparent affinity for each other, to spread out and become organized into parallel tracts through the monolayer.
研究分析了丁酸盐及相关短链脂肪酸对9 - 1C视黄酸反应性大鼠前列腺腺癌细胞的作用。9 - 1C细胞可被视黄酸诱导产生碱性磷酸酶（AP），也可被三到六个碳原子的脂肪酸诱导产生该酶。最有效的诱导剂是四碳脂肪酸丁酸盐，在2至10 mM的浓度范围内，它能使AP活性呈基本线性增加。丁酸盐和视黄酸对AP诱导作用的比较表明，视黄酸作为该酶的诱导剂，其效力要高出几个数量级。丁酸盐及相关短链脂肪酸还抑制9 - 1C细胞生长，而视黄酸在这些细胞中不会介导这种作用。丁酸盐浓度达到5 mM及以上时可实现完全生长抑制；1.5 mM可导致50%的抑制率。与AP诱导情况相同，所有三到六个碳原子的脂肪酸在一定程度上都能抑制生长，不过丁酸盐最为有效。脂肪酸诱导AP和抑制生长的碳链长度有效性顺序均为4＞5＞3＞6。丁酸盐在各种脂肪酸中似乎独特地能使细胞蛋白质增加。在4 mM丁酸盐存在下培养72小时的9 - 1C细胞，其蛋白质含量比对照细胞高出4倍多。这一观察结果与通过前向角光散射流式细胞术分析细胞体积的结果一致，该结果显示丁酸盐处理后9 - 1C细胞的横截面积呈浓度相关增加。最近的一项研究表明，这种效应也是由视黄酸介导的。丁酸盐处理最显著的作用之一是对细胞形态的影响。这种脂肪酸使通常以无序排列、彼此无明显亲和力生长的9 - 1C细胞展开，并通过单层排列成平行束状。
