Receptor activated Ca2+ release is inhibited by boric acid in prostate cancer cells

Kimberly Henderson, Salvatore L. Stella, Sarah Kobylewski, Curtis D. Eckhert

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background: The global disparity in cancer incidence remains a major public health problem. We focused on prostate cancer since microscopic disease in men is common, but the incidence of clinical disease varies more than 100 fold worldwide. Ca2+ signaling is a central regulator of cell proliferation, but has received little attention in cancer prevention. We and others have reported a strong dose-dependent reduction in the incidence of prostate and lung cancer within populations exposed to boron (B) in drinking water and food; and in tumor and cell proliferation in animal and cell culture models. Methods/Principal Findings: We examined the impact of B on Ca2+ stores using cancer and non-cancer human prostate cell lines, Ca2+ indicators Rhod-2 AM and Indo-1 AM and confocal microscopy. In DU-145 cells, inhibition of Ca2+ release was apparent following treatment with Ringers containing RyR agonists cADPR, 4CmC or caffeine and respective levels of BA (50 μM), (1, 10 μM) or (10, 20, 50,150 μM). Less aggressive LNCaP cancer cells required 20 μM BA and the non-tumor cell line PWR1E required 150 μM BA to significantly inhibit caffeine stimulated Ca2+ release. BA (10 μM) and the RyR antagonist dantroline (10 μM) were equivalent in their ability to inhibit ER Ca2+ loss. Flow cytometry and confocal microscopy analysis showed exposure of DU-145 cells to 50 mM BA for 1 hr decreased stored [Ca2+] by 32%. Conclusion/Significance: We show B causes a dose dependent decrease of Ca2+ release from ryanodine receptor sensitive stores. This occurred at BA concentrations present in blood of geographically disparate populations. Our results suggest higher BA blood levels lower the risk of prostate cancer by reducing intracellular Ca2+ signals and storage.

Original languageEnglish (US)
Article numbere6009
JournalPloS one
Volume4
Issue number6
DOIs
StatePublished - Jun 23 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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