title: CXCR4 and CXCL12 down-regulation: a novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers.
abstract: 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.
authors: Molecular Toxicology Interdepartmental Doctoral Program, University of California-Los Angeles, Los Angeles, CA 90095-1732, USA.
authors: Erin L
authors: EL
authors: Hsu
authors: Natalie
authors: N
authors: Chen
authors: Aya
authors: A
authors: Westbrook
authors: Feng
authors: F
authors: Wang
authors: Ruixue
authors: R
authors: Zhang
authors: Robert T
authors: RT
authors: Taylor
authors: Oliver
authors: O
authors: Hankinson
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology* / Q000517:prevention & control; D002417:Cattle; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D002633:Chemotaxis / Q000187:drug effects; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000517:prevention & control; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D012710:Serum Albumin, Bovine / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D054377:Chemokine CXCL12; D007211:Indoles; D019718:Receptors, CXCR4; D012710:Serum Albumin, Bovine; D004958:Estradiol; C016392:3,3'-diindolylmethane