Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines
Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines
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DOI：
10.1016/s0304-3835(97)00497-7
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发表时间：
1998-03-13
期刊：
影响因子：
9.7
通讯作者：
Nelson, MA
中科院分区：
文献类型：
--
作者：
Redman, C;Scott, JA;Nelson, MA
多年来，在流行病学和体外研究中，硒补充剂已被证明是一种抗癌剂。补充硒最近被证明可以降低癌症的总发病率。然而，硒作为抗癌剂的作用机制尚未阐明。在Clark等人的研究中，硒代蛋氨酸是膳食补充剂中硒的主要形式（Clark，L.C.，库姆斯，G.F.，Turnbull，W.B.，斯莱特，E.H.，Chalker，D.K.，Chow，J.，戴维斯，洛杉矶，格洛弗，R.A.，格雷厄姆，G.F.，真恶心E.G. Krongrad，A.，Lesher，J.L.，香港，Sanders，B. B.，史密斯，C.L.，泰勒，J.R.和癌症研究小组的营养预防（1996年）补充硒对皮肤癌患者癌症预防的影响：一项随机对照试验。J. Am.医学协会，276（24），1957-1963），因此我们评价了硒代甲硫氨酸对人肿瘤细胞的生长抑制作用。针对三种人肿瘤细胞系（MCF-7/S乳腺癌、DU-145前列腺癌细胞和UACC-375黑色素瘤）中的每一种和针对正常人二倍体成纤维细胞测试硒代蛋氨酸。所有细胞系均表现出硒代甲硫氨酸的剂量依赖性生长抑制方式。硒代甲硫氨酸在微摩尔（μ M）范围（范围从45至130 μ M）内抑制所有人肿瘤细胞系的生长，而正常二倍体成纤维细胞的生长抑制需要1 mM硒代甲硫氨酸，比癌细胞系高约1000倍。简而言之，正常二倍体成纤维细胞对硒代蛋氨酸的生长抑制作用不如癌细胞系敏感。此外，我们表明硒代蛋氨酸给药这些癌细胞系的凋亡细胞死亡和异常的有丝分裂的结果。这些结果表明肿瘤细胞和正常细胞对硒代蛋氨酸的敏感性不同。出版社：Elsevier Science爱尔兰有限公司
Selenium supplementation has been shown for many years to work as an anticarcinogenic agent both in epidemiology and in in vitro studies. Selenium supplementation has recently been shown to decrease total cancer incidence. However, the mechanism of action of selenium as an anticarcinogenic agent has yet to be elucidated. Selenomethionine was the predominant form of selenium in the dietary supplement in the study by Clark et al. (Clark, L.C., Combs, G.F., Turnbull, W.B., Slate, E.H., Chalker, D.K., Chow, J., Davis, L.S., Glover, R.A., Graham, G.F., Gross, E.G., Krongrad, A., Lesher, J.L., Park, H.K., Sanders, B.B., Smith, C.L., Taylor, J.R. and The Nutritional Prevention of Cancer Study Group (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. J. Am. Med. Assoc., 276 (24), 1957-1963) and therefore we evaluated the growth inhibitory effects of selenomethionine against human tumor cells. Selenomethionine was tested against each of three human tumor cell Lines (MCF-7/S breast carcinoma, DU-145 prostate cancer cells and UACC-375 melanoma) and against normal human diploid fibroblasts. All cell lines demonstrated a dose-dependent manner of growth inhibition by selenomethionine. Selenomethionine inhibited the growth of all of the human tumor cell lines in the micromolar (mu M) range (ranging from 45 to 130 mu M) while growth inhibition of normal diploid fibroblasts required 1 mM selenomethionine, approximately 1000-fold higher than for the cancer cell lines. In short, normal diploid fibroblasts were less sensitive than the cancer cell lines to the growth inhibitory effects of selenomethionine. Furthermore, we show that selenomethionine administration to these cancer cell Lines results in apoptotic cell death and aberrant mitoses. These results demonstrate the differential sensitivity of tumor cells and normal cells to selenomethionine. Published by Elsevier Science Ireland Ltd.