Bisphenol A stimulates human prostate cancer cell migration via remodelling of calcium signalling

Philippe Delcourt,Christian Slomianny,Jean-Louis Bonnal,Natalia Prevarskaya,Brigitte Mauroy,Morad Roudbaraki,Pierre Gosset,Sandra Derouiche,Marine Warnier,Pascal Mariot

doi:10.1186/2193-1801-2-54

Abstract

Bisphenol A (BPA), the principal constituent of reusable water bottles, metal cans, and plastic food containers, has been shown to be involved in human prostate cancer (PCa) cell proliferation. The aim of the present study was to explore the effect of BPA on PCa cell migration and the pathways involved in these processes. Using the transwell technique, we clearly show for the first time that the pre-treatment of the cells with BPA (1–10 nM) induces human PCa cell migration. Using a calcium imaging technique, we show that BPA pre-treatment induces an amplification of Store-Operated Calcium Entry (SOCE) in LNCaP cells. RT-PCR and Western blot experiments allowed the identification of the ion channel proteins which are up-regulated by BPA pre-treatments. These include the Orai1 protein, which is known as an important SOCE actor in various cell systems, including human PCa cells. Using a siRNA strategy, we observed that BPA-induced amplification of SOCE was Orai1-dependent. Interestingly, the BPA-induced PCa cell migration was suppressed when the calcium entry was impaired by the use of SOCE inhibitors (SKF96365, BTP2), or when the extracellular calcium was chelated. Taken together, the results presented here show that BPA induces PCa cells migration via a modulation of the ion channel protein expression involved in calcium entry and in cancer cell migration. The present data provide novel insights into the molecular mechanisms involved in the effects of an environmental factor on cancer cells and suggest both the necessity of preventive measures and the possibility of targeting ion channels in the treatment of PCa cell metastasis.

Highlights

Prostate cancer (PCa) is the most common non-cutaneous malignancy diagnosed in men and the metastatic PCa forms represent the second cause of mortality (Gronberg 2003; Jemal et al 2009)
For the first time, we investigated the impact of Bisphenol A (BPA) on human PCa cell migration and the mechanisms involved in the effects of BPA in these cells
We studied the impact of BPA on calcium signalling, on the expression of ion channels involved in Store-Operated Calcium Entry (SOCE) and human PCa cell migration in the absence of androgens

Summary

Introduction

Prostate cancer (PCa) is the most common non-cutaneous malignancy diagnosed in men and the metastatic PCa forms represent the second cause of mortality (Gronberg 2003; Jemal et al 2009). PCa requires androgen to survive and to proliferate; this dependence is exploited in the treatment of a disseminated disease, where androgen ablation is the first line of therapeutic intervention. These regimens are initially effective, tumors recur due to reactivation of Androgen. Accruing evidence indicates that exposure to environmental compounds, “endocrine disrupting compounds”, or EDCs, may adversely impact human health through multiple mechanisms, including alterations to the hormone receptor function (Henley and Korach 2006; Welshons et al 2003). A putative link has been established between an increased abundance of EDCs in the environment and rising hormone-dependent cancer incidence (Huff et al 1996). Recent investigations have placed particular emphasis on delineating the consequence of EDC exposure for various tissues including the reproductive tissues

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