title: Effects of decabrominated diphenyl ether (PBDE-209) in regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells.
abstract: BACKGROUND
  Polybrominated diphenyl ethers (PBDEs), commonly used in building materials, electronics, plastics, polyurethane foams, and textiles, are health hazards found in the environment.
  
  
  OBJECTIVE
  In this study we investigated the effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells as well as the underlying protein alterations.
  
  
  METHODS
  We used MCF-7 and MCF-7/ADR (multidrug-resistant MCF-7) breast cancer cell lines, the HeLa cervical cancer cell line, the OVCAR-3 ovarian cancer cell line, and the normal CHO (Chinese hamster ovary) cell line to assess the effects of PBDE-209 using cell viability, immunofluorescence, and flow cytometric assays. Western blot assays were used to detect changes in protein expression. To assess the effects of PBDE-209 on apoptosis, we used the protein kinase Cα (PKCα) inhibitor Gö 6976, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and tamoxifen.
  
  
  RESULTS
  Our data indicate that PBDE-209 increased viability and proliferation of the tumor cell lines and in CHO cells in a dose- and time-dependent manner. PBDE-209 also altered cell cycle distribution by inducing the S phase or G2/M phase. Furthermore, PBDE-209 partially suppressed tamoxifen-induced cell apoptosis in the breast cancer cell lines (MCF-7 and MCF-7/ADR) but suppressed Gö 6976- and PD98059-induced apoptosis in all cell lines. At the molecular level, PBDE-209 enhanced PKCα and ERK1/2 phosphorylation in the cell lines.
  
  
  CONCLUSIONS
  Our data demonstrate that PBDE-209 is able to promote proliferation of various cancer cells from the female reproductive system and normal ovarian CHO cells. Furthermore, it reduced tamoxifen, PKCα, and ERK inhibition-induced apoptosis. Finally, PBDE-209 up-regulated phosphorylation of PKCα and ERK1/2 proteins in tumor cells and in CHO cells.
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical College, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Li
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Jing-Si
authors.initials: JS
authors.lastname: Chen
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Huang
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Su
authors.forename: Fukang
authors.initials: F
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Dun-Jin
authors.initials: DJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013629:Tamoxifen / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D055768:Halogenated Diphenyl Ethers; D013629:Tamoxifen