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- Title
Effect of thimerosal on Ca<sup>2+</sup> movement and viability in human oral cancer cells.
- Authors
Kuo, L. N.; Huang, C. J.; Fang, Y. C.; Huang, C. C.; Wang, J. L.; Lin, K. L.; Chu, S. T.; Chang, H. T.; Chien, J. M.; Su, H. H.; Chi, C. C.; Chen, W. C.; Tsai, J. Y.; Liao, W. C.; Tseng, L. L.; Jan, C. R.
- Abstract
The effect of thimerosal on cytosolic free Ca2+ concentrations ([Ca2+]i) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca2+]i levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Thimerosal-induced Ca2+ influx was not blocked by L-type Ca2+ entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca2+-free medium, 50 μM thimerosal failed to induce a [Ca2+]i rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca2+]i rises. At concentrations between 5 and 10 μM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 μM thimerosal was potentiated by prechelating cytosolic Ca2+ with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1-7 μM thimerosal-induced apoptosis in a concentrationdependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx through non-L-type Ca2+ channels. Thimerosal killed cells in a concentrationdependent manner through apoptosis.
- Subjects
CANCER cells; ORAL cancer; PHOSPHOLIPASES; PROTEIN kinases; PROTEIN kinase C
- Publication
Human & Experimental Toxicology, 2009, Vol 28, Issue 5, p301
- ISSN
0960-3271
- Publication type
Article
- DOI
10.1177/0960327109106548