CXCR4 and CXCL12 down-regulation:: A novel mechanism for the chemoprotection of 3,3′-diindolylmethane for breast and ovarian cancers
CXCR4 and CXCL12 down-regulation:: A novel mechanism for the chemoprotection of 3,3′-diindolylmethane for breast and ovarian cancers
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DOI：
10.1016/j.canlet.2008.02.033
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发表时间：
2008-06-28
期刊：
影响因子：
9.7
通讯作者：
Hankinson, Oliver
中科院分区：
文献类型：
--
作者：
Hsu, Erin L.;Chen, Natalie;Hankinson, Oliver
十字花科蔬菜被认为可以预防多种癌症。 3,3'-二吲哚甲烷 (DIM) 是食用十字花科蔬菜时产生的酸催化产物，似乎对乳腺癌具有化学保护作用。已知趋化因子受体 CXCR4 及其独特配体 CXCL12 之间的相互作用可介导乳腺癌和其他癌症的进展和转移。这些癌症转移的器官会分泌 CXCL12，它与原发癌细胞表面表达的 CXCR4 结合。该过程随后刺激癌细胞的侵袭特性并将它们吸引到转移的首选器官部位。我们发现 DIM 在转录水平上以不依赖雌激素的方式下调 MCF-7 和 MDA-MB-231 乳腺癌细胞以及 BG-1 卵巢癌细胞中的 CXCR4 和 CXCL12。我们证明，MDA-MB-231 和 BG-1 细胞分别对 CXCL12 趋化和侵袭的潜力，但对 IL-6 或胎牛血清的趋化和侵袭潜力不受 DIM 抑制。此外，我们发现 DIM 在缺氧条件下下调 CXCR4，在雌二醇诱导条件下下调 CXCL12。我们的数据表明，DIM 预防乳腺癌、卵巢癌和可能其他癌症的一种机制是通过抑制 CXCR4 和/或 CXCL12，从而降低这些细胞的侵袭和转移潜力。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Cruciferous vegetables are thought to protect against numerous types of cancer. 3,3'-Diindolylmethane (DIM) is an acid-catalyzed product generated during the consumption of cruciferous vegetables and appears to be chemoprotective for breast cancer. The interaction between the chemokine receptor, CXCR4, and its unique ligand, CXCL12, is known to mediate the progression and metastasis of breast and other cancers. Organs to which these cancers metastasize secrete CXCL12, which binds to CXCR4 expressed on the Surface of primary cancer cells. This process subsequently stimulates the invasive properties of the cancer cells and attracts them to the preferred organ sites of metastases. We have found that DIM down-regulates both CXCR4 and CXCL12 in MCF-7 and MDA-MB-231 breast cancer cells as well as in BG-1 ovarian cancer cells at the transcriptional level and in an estrogen-independent manner. We demonstrate that the potential of MDA-MB-231 and BG-1 cells for chemotaxis and invasion towards CXCL12, but not towards IL-6 or fetal bovine serum, respectively, is inhibited by DIM. Furthermore, we show that DIM down-regulates CXCR4 under hypoxia and CXCL12 under estradiol-inducing conditions. Our data Suggest that one mechanism whereby DIM protects against breast, ovarian, and possibly other cancers is through the repression of CXCR4 and/or CXCL12, thereby lowering the invasive and metastatic potential of these cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.