Academic journal article Environmental Health Perspectives

Effects of Decabrominated Diphenyl Ether (PBDE-209) in Regulation of Growth and Apoptosis of Breast, Ovarian, and Cervical Cancer Cells

Academic journal article Environmental Health Perspectives

Effects of Decabrominated Diphenyl Ether (PBDE-209) in Regulation of Growth and Apoptosis of Breast, Ovarian, and Cervical Cancer Cells

Article excerpt

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 C[alpha] (PKC[alpha]) inhibitor Go 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 [G.sub.2]/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 Go 6976-and PD98059-induced apoptosis in all cell lines. At the molecular level, PBDE-209 enhanced PKC[alpha] 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, PKC[alpha], and ERK inhibition-induced apoptosis. Finally, PBDE-209 up-regulated phosphorylation of PKC[alpha] and ERK1/2 proteins in tumor cells and in CHO cells.

KEY WORDS: cell proliferation, ERK1/2, female reproductive cancer, PBDE-209, PKC[alpha]. Environ Health Perspect 120:541-546 (2012). [Online 6 January 2012]

Polybrominated diphenyl ethers (PBDEs) are flame retardants commonly used in an array of products, including construction materials, electronics, furnishings, plastics, polyurethane foams, and textiles (Brown et al. 2004). PBDEs are found in various environmental media (Bi et al. 2006; Guan et al. 2009; Thomsen et al. 2010) and are health hazards. They are toxic, persistent, and bioaccumulative and could induce endocrine-disrupting activity (Darnerud et al. 2001; Hamers et al. 2006, 2008; Richardson et al. 2008). Thus, the Stockholm Convention approved the elimination of their industrial production and use. Nevertheless, commercial PBDE mixtures are used without regulation in most Asian countries (Tan et al. 2007). Deca-PBDE is the only PBDE technical mixture currently produced in large quantities worldwide, a major component of which is PBDE congener 209 (La Guardia et al. 2006). Evidence indicates that PBDEs can cause neurobehavioral deficits and possibly cause cancer in experimental animals (McDonald 2002).

Molecularly, PBDEs elicit thyroxine-like and estrogen-like activity in vitro (Meerts et al. 2000). Barber et al. (2006) showed that low doses of PBDE ([10.sup.-12] to [10.sup.-9] M) induce growth kinetics and micronucleus formation in MCF-7 breast cancer cells. Llabjani et al. (2010, 2011) and Ukpebor et al. (2011) also found that low doses of PBDE induce MCF-7 cell proliferation. Mercado-Feliciano and Bigsby (2008) showed that the PBDE mixture DE-71 increases MCF-7 cell prolif-eration, which was prevented by antiestrogen treatment. PBDEs affect both male and female reproductive systems in vivo (Ceccatelli et al. 2006; Kuriyama et al. 2005; Lilienthal et al. 2006; Stoker et al. 2004; Talsness et al. 2005; Tseng et al. 2006). Metabolically, PBDE congeners PBDE-47, PBDE-85, and PBDE-99 are selectively taken up and retained in the liver, adrenal cortex, and ovaries after PBDE exposure in adult C57BL mice (Darnerud and Risberg 2006). …

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