Celecoxib-induced increase in cytosolic Ca2+ levels and apoptosis in HA59T human hepatoma cells
| Autor: | Cheng Js, Kuo Cc, Wei-Zhe Liang, Liu Si, He-Hsiung Cheng, Tseng Ll, Chi Cc, Lu Yc, Chung-Ren Jan, Chiang-Ting Chou, Lu T |
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| Rok vydání: | 2014 |
| Předmět: |
Carcinoma
Hepatocellular Thapsigargin Cell Survival Health Toxicology and Mutagenesis Antineoplastic Agents Apoptosis Phospholipase Biology Pharmacology Endoplasmic Reticulum Toxicology chemistry.chemical_compound BAPTA Cell Line Tumor Humans Protein kinase A Protein Kinase C Protein kinase C Sulfonamides Cyclooxygenase 2 Inhibitors Phospholipase C Endoplasmic reticulum Liver Neoplasms General Medicine chemistry Celecoxib Type C Phospholipases Pyrazoles Calcium |
| Zdroj: | Human & Experimental Toxicology. 33:1089-1098 |
| ISSN: | 1477-0903 0960-3271 |
| Popis: | Celecoxib has been shown to have antitumor effect in previous studies but the mechanisms are unclear. The effect of celecoxib on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in HA59T human hepatoma cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Celecoxib at concentrations of 10–50 μM induced a [Ca2+]i rise in a concentration-dependent manner. The response was reduced by 80% by removing Ca2+. Celecoxib induced Mn2+ influx, leading to quenching of fura-2 fluorescence. Celecoxib-evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C modulators. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin nearly abolished celecoxib-induced [Ca2+]i rise. Incubation with celecoxib abolished thapsigargin-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 abolished celecoxib-induced [Ca2+]i rise. At 1–50 μM, celecoxib inhibited cell viability by less than 20%, which was not reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N, N, N′, N′-tetraacetic acid/acetoxy methyl (BAPTA/AM). Celecoxib (10–50 μM) also induced apoptosis. In sum, in HA59T hepatoma cells, celecoxib induced a [Ca2+]i rise by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via protein kinase C-sensitive store-operated Ca2+ channels. Celecoxib also caused cell death via apoptosis. |
| Databáze: | OpenAIRE |
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