Effect of 2,4-Dimethylphenol on [Ca^(2+)]_i and Viability in PC3 Human Prostate Cancer Cells

Abstract

2,4-Dimethylphenol (DMP), a phenolic compound, evoked different physiological effects in various models. However, whether DMP induced Ca^(2+)-associated physiology is unclear in prostate cancer cells. This study examined the effect of DMP on cytosolic free Ca^(2+) concentrations ([Ca^(2+)]_i) and viability in PC3 human prostate cancer cells. DMP evoked [Ca^(2+)]_i rises concentration-dependently. DMP-evoked Ca^(2+) entry was inhibited by nifedipine, and the protein kinase C (PKC) modulators GF109203X and phorbol 12-myristate 13 acetate (PMA). In Ca^(2+)-free medium, treatment with the endoplasmic reticulum Ca^(2+) pump inhibitor thapsigargin [TG] or 2,5-di-tert-butylhy-droquinone (BHQ) abolished DMP-evoked [Ca^(2+)]_i rises. Conversely, treatment with DMP abolished thapsigargin or BHQ-evoked [Ca^(2+)]_i rises. Inhibition of phospholipase C (PLC) with U73122 abolished DMP-evoked [Ca^(2+)]_i rises. DMP at 200-700 μM decreased cell viability, which was not reversed by pretreatment with the Ca^(2+) chelator 1,2-bis(2- aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, DMP induced [Ca^(2+)]_i rises by evoking PLC-dependent Ca^(2+) release from the endoplasmic reticulum, and PKC-regulated, nifedipine-sensitive, non-store-operated Ca^(2+) entry. DMP also caused Ca^(2+)- independent cell death.