Diallyl disulfide induces Ca2+ mobilization in human colon cancer cell line SW480

摘要

Diallyl disulfide (DADS), one of the major organosulfur compounds of garlic, is recognized as a group of potential chemopreventive compounds. In this study, we examines the early signaling effects of DADS on human colorectal cancer cells SW480 loaded with Ca2+-sensitive dye fura-2. It was found that DADS caused an immediate and sustained rise of [Ca2+]_i in a concentration-dependent manner (EC₅₀ = 232 μM). DADS also induced a [Ca2+]_i elevation when extracellular Ca2+ was removed, but the magnitude was reduced by 45%. Depletion of intracellular Ca2+ stores with 2 μM carbonylcyanide m-chlorophenylhydrazone, a mitochondrial uncoupler, didn’t affect DADS’s effect. In Ca2+-free medium, the DADS-induced [Ca2+]_i rise was abolished by depleting stored Ca2+ with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). DADS-caused [Ca2+]_i rise in Ca2+-containing medium was not affected by modulation of protein kinase C activity. The DADS-induced Ca2+ influx was blocked by nicardipine (10 μM). U73122, an inhibitor of phospholipase C, abolished ATP (but not DADS)-induced [Ca2+]_i rise. These findings suggest that DADS induced a significant rise in [Ca2+]_i in SW480 colon cancer cells by stimulating both extracellular Ca2+ influx and thapsigargin-sensitive intracellular Ca2+ release via as yet unidentified mechanisms.