In:
Pharmacology, S. Karger AG, Vol. 88, No. 3-4 ( 2011), p. 201-212
Abstract:
〈 i 〉 Aims: 〈 /i 〉 The effect of the natural product thymol on cytosolic Ca 〈 sup 〉 2+ 〈 /sup 〉 concentrations ([Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 ) and viability in MG63 human osteosarcoma cells was examined. 〈 i 〉 Methods: 〈 /i 〉 The Ca 〈 sup 〉 2+ 〈 /sup 〉 -sensitive fluorescent dye fura-2 was applied to measure [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 . 〈 i 〉 Results: 〈 /i 〉 Thymol at concentrations of 200–1,000 µmol/l induced a [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 rise in a concentration-dependent fashion. The response was decreased partially by removal of extracellular Ca 〈 sup 〉 2+ 〈 /sup 〉 . Thymol-induced Ca 〈 sup 〉 2+ 〈 /sup 〉 entry was inhibited by nifedipine, econazole, SK & #38;F96365 and protein kinase C modulators. When extracellular Ca 〈 sup 〉 2+ 〈 /sup 〉 was removed, incubation with the endoplasmic reticulum Ca 〈 sup 〉 2+ 〈 /sup 〉 pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited the thymol-induced [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 rise. Incubation with thymol also inhibited the thapsigargin or BHQ-induced [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 rise. Inhibition of phospholipase C with U73122 abolished the thymol-induced [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 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 Ca 〈 sup 〉 2+ 〈 /sup 〉 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. 〈 i 〉 Conclusions: 〈 /i 〉 In MG63 cells, thymol induced a [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 rise by inducing phospholipase C-dependent Ca 〈 sup 〉 2+ 〈 /sup 〉 release from the endoplasmic reticulum and Ca 〈 sup 〉 2+ 〈 /sup 〉 entry via protein kinase C-sensitive store-operated Ca 〈 sup 〉 2+ 〈 /sup 〉 channels. Thymol induced cell death that may involve apoptosis via mitochondrial pathways.
Type of Medium:
Online Resource
ISSN:
0031-7012
,
1423-0313
Language:
English
Publisher:
S. Karger AG
Publication Date:
2011
detail.hit.zdb_id:
1483550-2
SSG:
15,3
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