{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:15:07Z","timestamp":1778814907790,"version":"3.51.4"},"reference-count":32,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2011]]},"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\u20131,000 \u00b5mol\/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\u2013600 \u00b5mol\/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\u2032,N\u2032-tetraacetic acid\/AM. Annexin V\/propidium iodide staining data suggest that thymol (200 and 400 \u00b5mol\/l) induced apoptosis in a concentration-dependent manner. Thymol (200 and 400 \u00b5mol\/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.<\/jats:p>","DOI":"10.1159\/000331864","type":"journal-article","created":{"date-parts":[[2011,10,5]],"date-time":"2011-10-05T07:05:15Z","timestamp":1317798315000},"page":"201-212","source":"Crossref","is-referenced-by-count":46,"title":["Effect of Thymol on Ca<sup>2+<\/sup> Homeostasis and Viability in MG63 Human Osteosarcoma 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