Boric acid is a modulator of stored calcium release in DU‐145 prostate cancer cells

Abstract

We have reported that both incidence and mortality of prostate cancer (PC) are decreased in a dose dependent manner by boron in diet (Oncology Rep 2004) and drinking water (Cancer Causes Control 2007). Boric acid (BA) inhibits PC cell proliferation (Cancer Lt 2004), binds to NAD+ and inhibits ADP ribosyl cyclase (J Mass Spec 2003,2004; J Chromatography 2006). Our present objective was to determine BA's effect on Ca2+ store release in DU‐145 cells. Endoplasmic reticulum (ER) Ca2+ was labeled with Rhod 2 and Ca2+ release was monitored using a Zeiss LSM 5 Pascal laser confocal microscope. BA inhibited Ca2+ release in response to 10 ìM cyclopiazonic acid (SERCA inhibitor) and 20 mM caffeine (ryanodine channel agonist) in a dose dependent manner beginning at 0.1 ìM BA. BA inhibited Ca2+ release in response to 4‐chloro‐m‐cresol in a dose dependent manner from 0.1 ìM BA to near complete inhibition at 10 ìM BA. Inhibition of caffeine induced Ca2+ release required >10 fold higher concentrations BA (150 ìM) in PWR1E non‐tumor cells than DU‐145 tumor cells. Our results demonstrate that BA acts as a ryanodine receptor antagonist and suggests boron's chemopreventative effect results from its ability to dampen ryanodine channel Ca2+ signaling. Funding: DAMD 17‐03‐1‐0067 and UC TSR&TP.