Abstract
Endocrine disrupting chemicals (EDC) are defined as environmental compounds that may result in adverse health problems such as cancer proliferaition and metastasis in humans. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and nonyl-phenol (NP) are known as typical EDCs. They are discharged from numerous industrial products including plastics, pesticides, drugs, detergents, and cosmetics. In this study, we examined the effect of BP-1 and NP on the growth of MCF-7 human breast cancer cells expressing oestrogen receptors (ER) in comparison with E2 to assess their risk in cancer progression. In cell viability assay, BP-1 (10–5, 10–6, and 10–7 M) and NP (10–6 and 10–7 M) were determined to induce the proliferation of MCF-7 cells as well as E2 (10–9 M) was compared to a negative control treated with DMSO (P < 0.05). Next, to confirm that BP-1 and NP increase growth and metastasis of MCF-7 cells, the alterations in transcriptional and translational levels of related markers, i.e. cyclin D1, p21, and cathepsin D, were examined by reverse-transcription (RT)-PCR and Western blot assay. Cyclin D1 is a factor responsible for G1/S cell cycle transition and p21 is a potent cyclin-dependent kinase (CDK) inhibitor that arrests cell cycle in G1 phase. Cathepsin D is one of the proteases that are responsible for cancer progression and metastasis. Treatment of MCF-7 breast cancer cells with BP-1 (10–5 M) or NP (10–6 M) resulted in up-regulation of cyclin D1 and cathepsin D and down-regulation of p21 at transcriptional and translational levels as well as E2 (10–9 M) compared to a negative control treated with DMSO (P < 0.05). In addition, E2, BP-1, or NP-induced alterations of these genes were reversed by the presence of ICI 182 780 (10–8 M), an ER antagonist, suggesting that the changes in these gene expressions may be regulated by ER-dependent signalling pathway. In conclusion, these results suggest that BP-1 and NP, like E2, may accelerate the growth of MCF-7 breast cancer cells by regulating cell-cycle-related genes through ER-mediated signalling pathway. Furthermore, these EDCs can adversely affect human health by promoting cancer metastasis through the amplification of cathepsin D via ER-dependent signalling pathway.
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