3,3′-diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer
3,3′-diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer
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DOI：
10.1016/j.bbrc.2005.12.059
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发表时间：
2006-02-10
影响因子：
3.1
通讯作者：
Tiwari, RK
中科院分区：
文献类型：
--
作者：
Garikapaty, VPS;Ashok, BT;Tiwari, RK
流行病学证据表明，前列腺癌（CaP）的进展和促进可通过饮食调节。由于所有男性都死于前列腺癌而不是疾病本身，因此通过化学预防策略来呈现或延缓疾病的进展是特别有趣的。我们一直在研究十字花科蔬菜中存在的化合物的抗癌特性，如吲哚-3-甲醇（13C）。二吲哚基甲烷（DIM）是13C的二聚体，在酸性条件下形成，与13C不同，它更稳定，具有更高的抗癌作用。在本报告中。我们证明，与13C相比，DIM在不依赖激素的DU 145 CaP细胞中是一种有效的药物。其抗前列腺癌作用是通过抑制Akt信号转导通路作为DIM介导的，与13C形成鲜明对比。诱导Akt下调。p-Akt。还有1113激酶。通过流式细胞术和下游细胞周期参数（如cyclin D1）的同步抑制，DIM还能诱导DU 145细胞G1阻滞。到。和cdk6。我们的数据表明，需要进一步开发DIM作为CaP的化学预防剂，这证明了流行病学证据和分子靶点是CaP传播/进展的决定因素。摄入DIM可能有利于Call患者，并通过消除可能存在的微转移来减少疾病复发，这些患者接受根治性前列腺切除术。(c) 2005爱思唯尔公司版权所有。
Epidemiological evidences suggest that the progression and promotion of prostate cancer (CaP) call be modulated by diet. Since all men die with prostate cancer rather than of the disease, it is of particular interest to present or delay the progression of the disease by chemopreventive strategies. We have been studying the anticancer properties of compounds present in cruciferous vegetables such as indole-3-carbinol (13C). Diindolylmethane (DIM) is a dimer of 13C that is formed under acidic Conditions Ond unlike 13C is more stable with higher anti-cancer effects. In the present report. we demonstrate that DIM is a potent agent compared to 13C ill the hormone independent DU 145 CaP cells. The anti-prostate cancer effect is mediated bN the inhibition of the Akt signal transduction pathway as DIM, in sharp contrast to 13C. induces the downregulation of Akt. p-Akt. and 1113 kinase. DIM also induced a G1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameter, such as cyclin D1. cdk4. and cdk6. Our data suggest a need for further development of DIM, as a chemopreventive agent for CaP, which justifies epidemiological evidences and molecular targets that are determinants for CaP dissemination/progression. The ingestion of DIM may benefit Call patients and reduce disease recurrence by eliminating micro-metastases that may be present ill patient, who undergo radical prostatectomy. (c) 2005 Elsevier Inc. All rights reserved.