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

Abstract

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.