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Ca(2+) mobilization induced by W-7 in MG63 human osteosarcoma cells
1Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Taiwan and Department of Biology and Institute of Life Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. crjan@isca.vghks.gov.tw
Pharmacological Research
|September 16, 2000
Summary
N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), a calmodulin inhibitor, increases intracellular calcium in osteosarcoma cells by releasing it from the endoplasmic reticulum and promoting influx. W-7 also demonstrates cytotoxicity, suggesting potential therapeutic applications.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Calmodulin inhibitors play a role in cellular signaling.
- Intracellular calcium ([Ca(2+)](i)) dynamics are crucial in cell function and disease.
- Osteosarcoma cells are a significant area of cancer research.
Purpose of the Study:
- To investigate the effects of W-7 on intracellular calcium levels in MG63 human osteosarcoma cells.
- To elucidate the mechanisms of W-7-induced calcium changes.
- To assess the cytotoxic potential of W-7 in osteosarcoma cells.
Main Methods:
- Utilized fura-2 as a calcium probe to measure intracellular free Ca(2+)levels.
- Administered W-7 in varying concentrations (20-1000 micro m) to MG63 cells.
- Manipulated extracellular calcium concentrations and used thapsigargin to study calcium release and influx pathways.
- Assessed cell viability using the trypan blue assay.
Main Results:
- W-7 induced a dose-dependent increase in [Ca(2+)](i) with an EC(50) of 100 micro m.
- Calcium signals comprised an initial rise and a sustained plateau.
- W-7 activated both intracellular calcium release (primarily from the endoplasmic reticulum) and extracellular calcium influx.
- W-7 demonstrated cytotoxic effects on osteosarcoma cells within 30 minutes.
Conclusions:
- W-7 modulates intracellular calcium homeostasis in human osteosarcoma cells through both release and influx mechanisms.
- The endoplasmic reticulum is a key source of W-7-mediated calcium release.
- W-7 exhibits cytotoxic activity against osteosarcoma cells, warranting further investigation for therapeutic potential.