Resveratrol is a natural compound that affects cellular calcium (Ca2+) homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in OC2 human oral cancer cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+]i, and water-soluble tetrazolium-1 was used to measure viability. Resveratrol evoked concentration-dependent increase in [Ca2+]i. The response was reduced by removing extracellular Ca2+. Resveratrol also caused manganese-induced fura-2 fluorescence quench. Resveratrol-evoked Ca2+ entry was inhibited by nifedipine and the protein kinase C (PKC) inhibitor GF109203X but was not altered by econazole, SKF96365, and the PKC activator phorbol 12-myristate 13 acetate. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di- tert-butylhydroquinone (BHQ) abolished resveratrol-evoked [Ca2+]i rise. Conversely, treatment with resveratrol inhibited BHQ-evoked [Ca2+]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished resveratrol-evoked [Ca2+]i rise. At 20–100 μM, resveratrol decreased cell viability, which was not affected by chelating cytosolic Ca2+with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-acetoxymethyl ester. Annexin V-fluorescein isothiocyanate staining data suggest that resveratrol at 20–40 μM induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, resveratrol induced [Ca2+]i rise by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and by causing Ca2+ entry via nifedipine-sensitive, PKC-regulated mechanisms. Resveratrol also caused Ca2+-independent apoptosis.

The effects of the environmental toxicant, triethyltin, on Ca2 + mobilization in Madin–Darby canine kidney (MDCK) cells have been examined. Triethyltin induced an increase in cytosolic free Ca2 + levels ([Ca2 +]i) at concentrations larger than 2 mM in a concentrationdependent manner. Within 5 min, the [Ca2 +]i signal was composed of a gradual rise and a sustained phase. The [Ca2 +]i signal was partly reduced by removing extracellular Ca2 +. In Ca2 +-free medium, pretreatment with thapsigargin (1 mM), an endoplasmic reticulum Ca2 + pump inhibitor, reduced 50 mM triethyltin-induced [Ca2 +]i increase by 80%. Conversely, pretreatment with triethyltin abolished thapsigargin-induced Ca2 + release. Pretreatment with U73122 (2 mM) to inhibit phospholipase C-coupled inositol 1,4,5-trisphosphate formations failed to alter 50 mM triethyltin-induced Ca2 + release. Incubation with triethyltin at a concentration (1 mM) that did not increase basal [Ca2 +]i for 3 min did not alter ATP (10 mM)and bradykinin (1 mM)-induced [Ca2 +]i increases. Collectively, this study shows that triethyltin altered Ca2 + movement in renal tubular cells by releasing Ca2 + from multiple stores in an inositol 1,4,5-trisphosphate-independent manner, and by inducing Ca2 + influx.

Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca2+) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca2+]i and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 μM and 300 μM, naproxen induced [Ca2+]i rises in a concentration-dependent manner. This Ca2+ signal was reduced partly when extracellular Ca2+ was removed. The Ca2+ signal was inhibited by a Ca2+ channel blocker nifedipine but not by store-operated Ca2+ channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca2+-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ pumps, partly inhibited naproxen-induced Ca2+ signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca2+]i rises. At concentrations between 15 μM and 30 μM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca2+]i rises by inducing Ca2+ release from multiple stores that included the endoplasmic reticulum and Ca2+ entry via nifedipine-sensitive Ca2+ channels. Naproxen induced cell death that involved apoptosis.

The anti-anginal drug fendiline induced internal Ca2+ release and external Ca2+ entry. Because prolonged increases in [Ca2+]i may lead to cell injury and death, the long-term effect of fendiline on the function of prostate cancer cells should be investigated.