Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Mutat Res. 2011 Jul-Oct;728(1-2):47-66. doi: 10.1016/j.mrrev.2011.06.001. Epub 2011 Jun 15.
Emerging evidence provide credible support in favor of the potential role of bioactive products derived from ingesting cruciferous vegetables such as broccoli, brussel sprouts, cauliflower and cabbage. Among many compounds, 3,3'-diindolylmethane (DIM) is generated in the acidic environment of the stomach following dimerization of indole-3-carbinol (I3C) monomers present in these classes of vegetables. Both I3C and DIM have been investigated for their use in preventing, inhibiting, and reversing the progression of cancer - as a chemopreventive agent. In this review, we summarize an updated, wide-ranging pleiotropic anti-tumor and biological effects elicited by DIM against tumor cells. It is unfeasible to point one single target as basis of cellular target of action of DIM. We emphasize key cellular and molecular events that are effectively modulated in the direction of inducing apoptosis and suppressing cell proliferation. Collectively, DIM orchestrates signaling through Ah receptor, NF-κB/Wnt/Akt/mTOR pathways impinging on cell cycle arrest, modulation of key cytochrome P450 enzymes, altering angiogenesis, invasion, metastasis and epigenetic behavior of cancer cells. The ability of DIM to selectively induce tumor cells to undergo apoptosis has been observed in preclinical models, and thus it has been speculated in improving the therapeutic efficacy of other anticancer agents that have diverse molecular targets. Consequently, DIM has moved through preclinical development into Phase I clinical trials, thereby suggesting that DIM could be a promising and novel agent either alone or as an adjunct to conventional therapeutics such as chemo-radio and targeted therapies. An important development has been the availability of DIM formulation with superior bioavailability for humans. Therefore, DIM appears to be a promising chemopreventive agent or chemo-radio-sensitizer for the prevention of tumor recurrence and/or for the treatment of human malignancies.
越来越多的证据为十字花科蔬菜（如花椰菜、西兰花、白菜和甘蓝等）中生物活性产物的潜在作用提供了可信的支持，这些生物活性产物可通过摄入这些蔬菜而产生。在许多化合物中，3,3'-二吲哚甲烷（DIM）是在这些蔬菜类中存在的吲哚-3-甲醇（I3C）单体二聚化后在胃的酸性环境中生成的。I3C 和 DIM 都已被研究用于预防、抑制和逆转癌症的进展——作为一种化学预防剂。在这篇综述中，我们总结了 DIM 对肿瘤细胞产生的最新的、广泛的、多效性的抗肿瘤和生物学作用。指出 DIM 作为细胞作用靶点的基础是不切实际的。我们强调了有效调节细胞凋亡和抑制细胞增殖方向的关键细胞和分子事件。总之，DIM 通过 Ah 受体、NF-κB/Wnt/Akt/mTOR 途径协调信号转导，影响细胞周期停滞、关键细胞色素 P450 酶的调节、血管生成、侵袭、转移和癌细胞的表观遗传行为。在临床前模型中观察到 DIM 选择性诱导肿瘤细胞凋亡的能力，因此有人推测，它可以改善其他具有多种分子靶点的抗癌药物的治疗效果。因此，DIM 已经从临床前开发进入 I 期临床试验，这表明 DIM 可能是一种有前途的新型药物，无论是单独使用还是作为常规治疗（如化疗、放疗和靶向治疗）的辅助药物。一个重要的进展是为人类提供了具有更高生物利用度的 DIM 制剂。因此，DIM 似乎是一种有前途的化学预防剂或化学放疗增敏剂，可用于预防肿瘤复发和/或治疗人类恶性肿瘤。
