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- Title
Effect of Thymol on Ca Homeostasis and Viability in MG63 Human Osteosarcoma Cells.
- Authors
Chang, Hong-Tai; Hsu, Shu-Shong; Chou, Chiang-Ting; Cheng, Jin-Shiung; Wang, Jue-Long; Lin, Ko-Long; Fang, Yi-Chien; Chen, Wei-Chuan; Chien, Jau-Min; Lu, Ti; Pan, Chih-Chuan; Cheng, He-Hsiung; Huang, Jong-Khing; Kuo, Chun-Chi; Chai, Kuo-Liang; Jan, Chung-Ren
- Abstract
Aims: The effect of the natural product thymol on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells was examined. Methods: The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Results: Thymol at concentrations of 200-1,000 μmol/l induced a [Ca2+]i rise in a concentration-dependent fashion. The response was decreased partially by removal of extracellular Ca2+. Thymol-induced Ca2+ entry was inhibited by nifedipine, econazole, SK&F96365 and protein kinase C modulators. When extracellular Ca2+ was removed, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited the thymol-induced [Ca2+]i rise. Incubation with thymol also inhibited the thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 abolished the thymol-induced [Ca2+]i rise. At concentrations of 100-600 μmol/l, thymol killed cells in a concentration-dependent manner. This cytotoxic effect was not changed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid/AM. Annexin V/propidium iodide staining data suggest that thymol (200 and 400 μmol/l) induced apoptosis in a concentration-dependent manner. Thymol (200 and 400 μmol/l) also increased levels of reactive oxygen species. Conclusions: In MG63 cells, thymol induced a [Ca2+]i rise by inducing phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via protein kinase C-sensitive store-operated Ca2+ channels. Thymol induced cell death that may involve apoptosis via mitochondrial pathways. Copyright © 2011 S. Karger AG, Basel
- Subjects
THYMOL; PHARMACODYNAMICS; CALCIUM; HOMEOSTASIS; OSTEOSARCOMA; REACTIVE oxygen species; PROTEIN kinase C
- Publication
Pharmacology, 2011, Vol 88, Issue 3/4, p201
- ISSN
0031-7012
- Publication type
Article
- DOI
10.1159/000331864