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

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.

Low‐Dose Bisphenol A Exposure: A Seemingly Instigating Carcinogenic Effect on Breast Cancer

“…A recent study showed BPA treatment increased the levels of Orai1 protein, a Ca 2+ selective ion channel, and subsequently stimulate prostate cancer cell migration 163. This finding suggests involvement of BPA in regulating ion channel expression and function, a mechanism through which breast cancer may be initiated or progressed.…”

Effects of Bisphenol A on ion channels: Experimental evidence and molecular mechanisms

“…A recent study has reported an increase in Orai1 protein levels induced by low doses of BPA (1-10 nM) in prostate cancer cells, leading to an amplification of the store operated Ca 2+ entry and stimulating cancer cell migration [38]. These results provide novel insights into the molecular mechanisms involved in the effects of an environmental factor on cancer cells.…”

Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration

“…BPA regulates the expression of an important component of SOCE: Orai1 (but not STIM1), and also other channels, such as TRPV6 and Ca 2+ -activated potassium channels BKca and IKca in LNCaP cells. The inhibition of SOCE reduces the migration of androgen-dependent or -independent prostate cells [79].…”