Protective effects of tacrine and donepezil against staurosporine-induced apoptotic death / 药学学报
Acta Pharmaceutica Sinica
;
(12): 98-102, 2002.
Article
in Chinese
| WPRIM
| ID: wpr-343392
ABSTRACT
<p><b>AIM</b>To study whether tacrine and donepezil can prevent cell apoptosis induced by staurosporine in NG108-15 and Hela cell lines.</p><p><b>METHODS</b>MTT assay was used to examine if staurosporine impairs cell metabolism. Phase-contrast and fluorescence microscope were used to examine cell morphological changes. DNA was isolated and electrophoretically separated on 1% agarose gel to observe if there were DNA fragments. Western blot was made to analyse protein levels of anti-apoptotic Bcl-2 and proapoptotic Bax.</p><p><b>RESULTS</b>NG108-15 cells treated with 0.1 mumol.L-1 staurosporine for 12-24 hours exhibited marked cell death and DNA fragmentation. Pre-treatment with 0.1 mmol.L-1 tacrine provided approximately 40% protective effect and resulted in obvious inhibition or delay of DNA fragmentation. Moreover, NG108-15 cells treated with tacrine became elongated and polarized, and showed longer processes than control cells. Pretreatment with 0.1 mmol.L-1 tacrine significantly increased the expression of Bcl-2 protein level and delayed the staurosporine-induced increase of Bax protein expression. However, donepezil did not show any protective effect on the cell impairment induced by staurosporine in NG108-15 cells. In Hela cells 0.1 mumol.L-1 staurosporine also induced significant cell injury, but pretreatment with tacrine and donepezil did not provide any obvious protective effect against this cell damage.</p><p><b>CONCLUSION</b>Donepezil did not provide obvious protective effect against apoptosis, and protective effects of tacrine might not be mediated through AChE inhibition. Protective effects of tacrine against staurosporine-induced injury might be selective to different cells.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Piperidines
/
Tacrine
/
HeLa Cells
/
Cholinesterase Inhibitors
/
Apoptosis
/
Staurosporine
/
Protective Agents
/
Glioma
/
Hybrid Cells
Limits:
Animals
/
Humans
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2002
Type:
Article
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