The garlic ingredient diallyl sulfide induces Ca(2+) mobilization in Madin-Darby canine kidney cells

Diallyl sulfide (DAS), one of the major organosulfur compounds (OSCs) of garlic, is recognized as a group of potential chemoproventive compounds. In this study, we examines the early signaling effects of DAS on renal cells loaded with Ca(2+)-sensitive dye fura-2. It was found that DAS caused an immediate and sustained rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50)=2.32 mM). DAS also induced a [Ca(2+)](i) elevation when extracellular Ca(2+) was removed, but the magnitude was reduced by 45%. Depletion of intracellular Ca(2+) stores with CCCP, a mitochondrial uncoupler, did not affect DAS's effect. In Ca(2+)-free medium, the DAS-induced [Ca(2+)](i) rise was abolished by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). DAS-caused [Ca(2+)](i) rise in Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The DAS-induced Ca(2+) influx was blocked by nicardipine. U73122, an inhibitor of phospholipase C, abolished ATP (but not DAS)-induced [Ca(2+)](i) rise. Additionally, pretreatment with DAS for 24 h decreased cell viability in a concentration-dependent manner. Furthermore, DAS-induced cell death involved apoptotic events. These findings suggest that diallyl sulfide induced a significant rise in [Ca(2+)](i) in MDCK renal tubular cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms.