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Diallyl disulfide induces Ca2+ mobilization in human colon cancer cell line SW480
Chung-Yi Chen1, Chien-Fu Huang, Ya-Ting Tseng
1Department of Medical Laboratory Science and Biotechnology, School of Medical and Health Sciences, Fooyin University, 151 Chinhsueh Rd, Ta-Liao District, Kaohsiung City, 83102, Taiwan.
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 Ca(2+)-sensitive dye fura-2. It was found that DADS caused an immediate and sustained rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 232 μM). DADS 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 2 μM carbonylcyanide m-chlorophenylhydrazone, a mitochondrial uncoupler, didn't affect DADS's effect. In Ca(2+)-free medium, the DADS-induced [Ca(2+)](i) rise was abolished by depleting stored Ca(2+) with 1 μM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). DADS-caused [Ca(2+)](i) rise in Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The DADS-induced Ca(2+) influx was blocked by nicardipine (10 μM). U73122, an inhibitor of phospholipase C, abolished ATP (but not DADS)-induced [Ca(2+)](i) rise. These findings suggest that DADS induced a significant rise in [Ca(2+)](i) in SW480 colon cancer cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms.
Insights
Diallyl disulfide (DADS), a garlic compound, increases intracellular calcium in colorectal cancer cells. This occurs through both calcium influx and release from internal stores, suggesting potential chemopreventive mechanisms.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Diallyl disulfide (DADS) is a key organosulfur compound found in garlic, recognized for its potential chemopreventive properties.
- Colorectal cancer (CRC) remains a significant global health challenge, necessitating research into novel therapeutic and preventive strategies.
- Understanding the early cellular signaling events triggered by chemopreventive agents is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the early signaling effects of Diallyl disulfide (DADS) on intracellular calcium dynamics in human colorectal cancer cells (SW480).
- To elucidate the mechanisms by which DADS influences intracellular calcium levels, including contributions from extracellular influx and intracellular stores.
- To explore the potential role of DADS in modulating calcium signaling pathways relevant to cancer chemoprevention.
Main Methods:
- Utilized human colorectal cancer SW480 cells loaded with the calcium-sensitive dye fura-2 to monitor intracellular calcium concentrations ([Ca(2+)](i)).
- Administered varying concentrations of DADS and employed specific inhibitors (nicardipine, thapsigargin, U73122) and conditions (Ca(2+)-free medium) to dissect calcium signaling pathways.
- Assessed the impact of DADS on calcium influx, intracellular calcium store release, and the involvement of mitochondrial and endoplasmic reticulum stores.
Main Results:
- DADS induced a rapid and sustained, concentration-dependent increase in intracellular calcium ([Ca(2+)](i)) in SW480 cells (EC(50) = 232 μM).
- DADS-stimulated calcium elevation involved both extracellular calcium influx and release from thapsigargin-sensitive intracellular stores, with a 45% reduction observed when extracellular calcium was removed.
- The DADS-induced calcium rise was independent of mitochondrial uncoupling and protein kinase C activity, but the influx component was sensitive to nicardipine.
Conclusions:
- Diallyl disulfide (DADS) significantly elevates intracellular calcium in colorectal cancer cells SW480.
- DADS activates both extracellular calcium influx and thapsigargin-sensitive intracellular calcium release mechanisms.
- These calcium signaling modulations by DADS may underlie its potential chemopreventive effects in colorectal cancer.
