Telang N T, Katdare M, Bradlow H L, Osborne M P, Fishman J
Strang Cancer Research Laboratory and Rockefeller University, New York, New York 10021, USA.
Proc Soc Exp Biol Med. 1997 Nov;216(2):246-52. doi: 10.3181/00379727-216-44174.
Aberrant proliferation is an early-occurring intermediate event in carcinogenesis whose inhibition may represent preventive intervention. Indole-3-carbinol (I3C), a glucosinolate metabolite from cruciferous vegetables, inhibits organ site carcinogenesis in rodent models. Clinically relevant biochemical and cellular mechanisms for the anticarcinogenic effects of I3C, however, remain unclear. Experiments were conducted on reduction mammoplasty derived 184-B5 cells initiated with chemical carcinogen (184-B5/BP) or with oncogene (184-B5/HER), and on mammary-carcinoma-derived MDA-MD-231 cells to examine whether (i) I3C inhibits aberrant proliferation in initiated and transformed cells, and (ii) inhibition of aberrant proliferation is associated with altered cell-cycle progression, estradiol (E2) metabolism, and apoptosis. Aberrant proliferation in 184-B5/BP, 184-B5/HER, and MDA-MB-231 cells was evident by a 55%-67% decrease in the ratio of quiescent (Q = G0) to proliferative (P = S + M) phase of the cell cycle, a 72%-90% decrease in apoptosis, and a 76%-106% increase in anchorage-dependent growth. These cells also exhibited a 88%-90% decrease in the ratio of C2 to C16alpha-hydroxylation products of E2. Treatment of 184-B5/BP, 184-B5/HER, and MDA-MB-231 cells to cytostatic dose of 50 microM I3C resulted in an 137%-210% increase in Q/P I3C ratio, a 4- to 18-fold increase in E2 metabolite ratio, a 2-fold increase in cellular apoptosis, and a 54%-61% inhibition of growth. The preventive efficacy of I3C on human mammary carcinogenesis may be due in part to its ability to regulate cell-cycle progression, increase the formation of antiproliferative E2 metabolite, and induce cellular apoptosis.
异常增殖是致癌过程中早期出现的中间事件，抑制异常增殖可能是一种预防性干预措施。吲哚 - 3 - 甲醇（I3C）是十字花科蔬菜中的硫代葡萄糖苷代谢产物，可抑制啮齿动物模型中的器官部位致癌作用。然而，I3C抗癌作用的临床相关生化和细胞机制仍不清楚。本研究以化学致癌物（184 - B5/BP）或癌基因（184 - B5/HER）启动的缩乳术来源的184 - B5细胞，以及乳腺癌来源的MDA - MD - 231细胞为实验对象，研究（i）I3C是否抑制起始细胞和转化细胞中的异常增殖，以及（ii）异常增殖的抑制是否与细胞周期进程、雌二醇（E2）代谢和细胞凋亡的改变有关。184 - B5/BP、184 - B5/HER和MDA - MB - 231细胞中的异常增殖表现为细胞周期静止期（Q = G0）与增殖期（P = S + M）的比例降低55% - 67%，细胞凋亡减少72% - 90%，贴壁依赖性生长增加76% - 106%。这些细胞中E2的C2与C16α - 羟基化产物的比例也降低了88% - 90%。用50μM的细胞生长抑制剂量的I3C处理184 - B5/BP、184 - B5/HER和MDA - MB - 231细胞，导致Q/P I3C比例增加137% - 210%，E2代谢产物比例增加4至18倍，细胞凋亡增加2倍，生长抑制54% - 61%。I3C对人类乳腺癌发生的预防作用可能部分归因于其调节细胞周期进程、增加抗增殖E2代谢产物形成以及诱导细胞凋亡的能力。
