Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic.
Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic.
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DOI：
10.1016/j.mrrev.2011.06.001
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发表时间：
2011-07
影响因子：
5.3
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Banerjee, Sanjeev;Kong, Dejuan;Wang, Zhiwei;Bao, Bin;Hillman, Gilda G.;Sarkar, Fazlul H.
新出现的证据提供了可信的支持，有利于来自十字花科蔬菜，如花椰菜，抱子甘蓝，花椰菜和卷心菜的生物活性产品的潜在作用。在许多化合物中，3，3 ′-二吲哚基甲烷（DIM）是在胃的酸性环境中，在这些类别的蔬菜中存在的吲哚-3-甲醇（I3 C）单体二聚化后产生的。已经研究了I3 C和DIM作为化学预防剂在预防、抑制和逆转癌症进展中的用途。本文就近年来DIM对肿瘤细胞的多效抗肿瘤作用及生物学效应作一综述。指出一个单一的靶点作为DIM作用的细胞靶点的基础是不可行的。我们强调在诱导凋亡和抑制细胞增殖的方向上有效调节的关键细胞和分子事件。总的来说，DIM通过Ah受体、NF-κB/Wnt/Akt/mTOR途径协调信号传导，影响细胞周期停滞、调节关键细胞色素P450酶、改变癌细胞的血管生成、侵袭、转移和表观遗传行为。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，因此推测其可改善具有不同分子靶点的其他抗癌药物的疗效。因此，DIM已经通过临床前开发进入I期临床试验，从而表明DIM可以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方法（如化学-放射治疗和靶向治疗）的辅助治疗。一个重要的发展是具有上级人体生物利用度的DIM制剂的可用性。因此，DIM似乎是用于预防肿瘤复发和/或用于治疗人类恶性肿瘤的有前景的化学预防剂或化学-放射增敏剂。
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 behaviors 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 therapy, 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.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1158/1940-6207.capr-08-0142
发表时间：
2009-06
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bhatnagar N;Li X;Chen Y;Zhou X;Garrett SH;Guo B
通讯作者：
Guo B
影响因子：
5.7
作者：
Ali, Shadan;Banerjee, Sanjeev;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
4
作者：
Ahmad, Aamir;Kong, Dejuan;Wang, Zhiwei;Sarkar, Sanila. H.;Banerjee, Sanjeev;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
4.7
作者：
Chang, XF;Firestone, GL;Bjeldanes, LF
通讯作者：
Bjeldanes, LF