Diindolilmethane (DIM) selectively inhibits cancer stem cells

作者：Alexandre Semov, Ludmila Iourtchenco, Лиу Лин Фанг, Li Shengmin, Yan Xu, Xiaoxue Su, Ekaterina Muyjnek, В. И. Киселев, Valery Yu. Alakhov · 发表于：Biochemical and Biophysical Research Communications · 年份：2012 · DOI：10.1016/j.bbrc.2012.06.062 · 被引用次数：35 · 研究领域：Genomics, phytochemicals, and oxidative stress、Cancer Cells and Metastasis、Polyamine Metabolism and Applications

Epidemiologic studies repeatedly have shown chemopreventive effects of cruciferous vegetables. Indole-3-carbinol (I3C) and its metabolite diindolylmethane (DIM) were identified in these plants as active ingredients and theirs anti-tumor activities were confirmed in multiple in vitro and in vivo experiments. Here, we demonstrate that DIM is a selective and potent inhibitor of cancer stem cells (CSCs). In several cancer cell lines, DIM inhibited tumor sphere formation at the concentrations 30-300 times lower than concentrations required for growth inhibition of parental cells cultured as adherent culture. We also found that treatment with DIM overcomes chemoresistance of CSCs to cytotoxics, such as paclitaxel, doxorubicin, and SN-38. Pre-treatment of tumor spheres with DIM before implantation to mice significantly retarded the growth of primary tumors compared to tumors formed by untreated tumor spheres. The concentrations of DIM required to suppress CSCs formation are in the close range to those achievable in human plasma after oral dosing of the compound. Therefore, DIM can potentially be used in cancer patients, either alone, or in combinations with existing drugs.