SELECTIVE RESPONSIVENESS OF HUMAN BREAST-CANCER CELLS TO INDOLE-3-CARBINOL, A CHEMOPREVENTIVE AGENT
SELECTIVE RESPONSIVENESS OF HUMAN BREAST-CANCER CELLS TO INDOLE-3-CARBINOL, A CHEMOPREVENTIVE AGENT
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DOI：
10.1093/jnci/86.2.126
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发表时间：
1994-01-19
期刊：
影响因子：
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通讯作者：
OSBORNE, MP
中科院分区：
文献类型：
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作者：
TIWARI, RK;GUO, L;OSBORNE, MP
背景资料：吲哚-3-甲醇（I3 C）是一种在卷心菜、花椰菜和布鲁塞尔子甘蓝中发现的化合物，当喂给某些品系的小鼠时，它能抑制乳腺肿瘤的生长。I3 C的化学预防和抗肿瘤作用取决于物种和组织类型。对I3 C有反应的作用机制和特定的人类细胞类型尚不清楚。目的：我们的目的是研究I3 C在雌激素反应性（MCF-7）和雌激素非反应性（MDAMB 231）人乳腺癌细胞系中的作用机制。方法：雌激素反应性通过雌二醇刺激去除雌激素的乳腺癌细胞生长的能力来确定。测量I3 C对细胞生长、雌二醇代谢和细胞色素P-4501 A1水平的影响。通过细胞计数和软琼脂测定法测量生长，通过放射性测定法检查雌激素代谢，并通过用多克隆抗体的Western印迹法测量细胞色素P-4501 A1的水平。结果：I3 C对雌激素敏感细胞MCF-7的生长有抑制作用，而对雌激素非敏感细胞MDA-MB-231的生长无明显影响。在MCF-7细胞中，I3 C增强了雌激素的特异性C-2羟基化和细胞色素P-4501 A1的诱导，但在MDA-MB-231细胞中没有。结论：I3 C对人乳腺癌细胞具有特异性的抑制作用。I3 C的抑制作用可能涉及选择性诱导雌二醇代谢和相关的细胞色素P-450系统，这可能仅限于雌激素敏感细胞。
Background: Indole-3-carbinol (I3C), a compound found in cabbage, broccoli, and brussels sprouts, inhibits the growth of mammary tumors when fed to certain strains of mice. The chemopreventive and antitumor effects of I3C depend on the species and tissue type. The mechanism of action and specific human cell types that respond to I3C are not known. Purpose: Our purpose was to study the mechanism of action of I3C in estrogen-responsive (MCF-7) and estrogen-nonresponsive (MDAMB231) human breast cancer cell lines. Methods: Estrogen responsiveness was determined by the ability of estradiol to stimulate the growth of breast cancer cells deprived of estrogen. The effect- of I3C was measured on cell growth, estradiol metabolism, and level of cytochrome P-4501A1. Growth was measured by cell counts and soft-agar assay, estrogen metabolism was examined by a radiometric assay, and the level of cytochrome P-4501A1 was measured by Western blots with a polyclonal antibody. Results: I3C inhibits the growth of estrogen-responsive cell line MCF-7 but has little effect on estrogen-nonresponsive cell line MDA-MB-231. Specific C-2 hydroxylation of estrogen and induction of cytochrome P-4501A1 was enhanced by I3C in the MCF-7 but not in the MDA-MB-231 cells. Conclusion: I3C has specific antigrowth effects in human breast cancer cells. The inhibitory effects of I3C may involve selective induction of estradiol metabolism and the related cytochrome P-450 system that may be limited to estrogen-sensitive cells.