Resveratrol induces intracellular Ca2+rise via T-type Ca2+channels in a mesothelioma cell line

Aims Intracellular calcium (Ca2+) is known to play an important role in cancer development and growth. Resveratrol (Res) is a stilbene polyphenol occurring in several plant species and known for various possible beneficial effects, including its ability to inhibit proliferation and to induce apoptosis in cancer cells. This study was designed to determine whether Res affects Ca2+signaling in cancer cells. Main methods We used the REN human mesothelioma cell line, as an in vitro cancer cell model, and the non-malignant human mesothelial MeT5A cell line, as normal cell model. Cytosolic Ca2+concentration was measured by the fluorescent indicator Fura-2. Immunofluorescence, Western blot, and siRNA technique were employed to assess the involvement of T-type Ca2 +channels. Cell viability was determined by the calcein assay. Key findings REN cells transiently exposed to 1-10 μM Res showed increasing peaks of Ca2+that were absent in Ca2+-free medium and were reduced by non-selective (Ni2+), and highly selective (NNC 55-0396) T-type Ca2+channels antagonist, and by siRNA knockout of Cav3.2 T-type Ca2+channel gene. Dose-dependent curve of Res-induced Ca2+peaks showed a rightward shift in normal MeT-5 A mesothelial cells (EC50= 4.9 μM) with respect to REN cells (EC50= 2.7 μM). Moreover, incubation with 3 and 10 μM Res for 7 days resulted in cell growth inhibition for REN, but not for MeT-5 A cells. Significance Res induces Ca2+influx, possibly mediated through T-type Ca2+channels, with significant selectivity towards mesothelioma cells, suggesting a possible use as an adjuvant to chemotherapy drugs for mesothelioma clinical treatment.