engleski

Lithium increases expression of p21WAF/Cip1 and survivin in human glioblastoma cells

Lithium is the most widely prescribed mood stabilizer, but the precise molecular mechanisms underlying its therapeutic function are not yet quite eucidated. Recent preclinical and clinical evidence indicate its neuroprotective and neurotrophic effects. As a tight coupling of function and metabolism in the central nervous system between glial cells and neurons has been recently detected, lithium effect on glial cells may participate also in total beneficial effects of this drug. The aim of the present study was to analyze molecular mechanisms induced in human glioblastoma A1235 cells by the treatment with lithium, especially its influence on the expression of apoptosis related genes. Lower levels of lithium (0.5 mM and 2 mM) did not cause any cytotoxicity or changes in the cell cycle phase distribution following 72h inbubation. However, higher dose (20 mM) was cytostatic for glioblastoma cells, and caused accumulation of cells in G2/M phase of the cell-cycle. The treatment with lithium did not alter the levels of Bcl-2, procaspase-3 and didn't cleave PARP, but increased the levels of p21WAF/Cip1 and survivin. Thus, increased expression of p21WAF/Cip (a protein with anti-apoptotic function), and survivin (a protein that supports the growth of cells by suppression of apoptosis and promoting cell proliferation), can be the early events in the long-term cell response to lithium, that may be involved in the beneficial effects of this drug.

apoptosis; glioblastoma cells; lithium; p21WAF/Cip1; survivin

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