title: Resveratrol induces intracellular Ca(2+) rise via T-type Ca(2+) channels in a mesothelioma cell line.
abstract: OBJECTIVE
  Intracellular calcium (Ca(2+)) 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 Ca(2+) signaling in cancer cells.
  
  
  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 Ca(2+) concentration was measured by the fluorescent indicator Fura-2. Immunofluorescence, Western blot, and siRNA technique were employed to assess the involvement of T-type Ca(2+) channels. Cell viability was determined by the calcein assay.
  
  
  RESULTS
  REN cells transiently exposed to 1-10μM Res showed increasing peaks of Ca(2+) that were absent in Ca(2+)-free medium and were reduced by non-selective (Ni(2+)), and highly selective (NNC 55-0396) T-type Ca(2+) channels antagonist, and by siRNA knockout of Cav3.2T-type Ca(2+) channel gene. Dose-dependent curve of Res-induced Ca(2+) peaks showed a rightward shift in normal MeT-5A mesothelial cells (EC50=4.9μM) with respect to REN cells (EC50=2.7μM). Moreover, incubation with 3 and 10μM Res for 7days resulted in cell growth inhibition for REN, but not for MeT-5A cells.
  
  
  CONCLUSIONS
  Res induces Ca(2+) influx, possibly mediated through T-type Ca(2+) channels, with significant selectivity towards mesothelioma cells, suggesting a possible use as an adjuvant to chemotherapy drugs for mesothelioma clinical treatment.
authors: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, via De Marini 6, 16149 Genova, Italy. Electronic address: marchetti@ge.ibf.cnr.it.
authors: Carla
authors: C
authors: Marchetti
authors: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, viale T. Michel 11, 15121 Alessandria, Italy.
authors: Stefania
authors: S
authors: Ribulla
authors: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, viale T. Michel 11, 15121 Alessandria, Italy.
authors: Valeria
authors: V
authors: Magnelli
authors: Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, viale T. Michel 11, 15121 Alessandria, Italy.
authors: Mauro
authors: M
authors: Patrone
authors: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, via De Marini 6, 16149 Genova, Italy; Dipartimento di Scienze e Innovazione Tecnologica (DISIT), Università del Piemonte Orientale, viale T. Michel 11, 15121 Alessandria, Italy.
authors: Bruno
authors: B
authors: Burlando
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism*; D008654:Mesothelioma / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D013267:Stilbenes; D000077185:Resveratrol; D002118:Calcium
keywords: Cav3.2 Ca(2+) channels; Cell growth inhibition; Cytosolic Ca(2+); Fura-2; Mesothelial Met5A cells; Mesothelioma REN cells