RRML - S-Adenosylmethionine - induced cytotoxicity in glioblastoma cells does not affect the Igf-1r methylation
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Dr. Adrian Man

   
 
Nr. 18(3)/2010
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S-Adenosylmethionine - induced cytotoxicity in glioblastoma cells does not affect the Igf-1r methylation

Roxana Ola, Iulia D., Ioana Berindan, Ovidiu Bălăcescu, Mihai Bănicioiu, Anica Dricu


Abstract:

Despite treatment consisting of intensive multimodality therapy, glioblastoma (GB) patients have a very poor prognosis explaining the need of searching for novel therapeutic approaches. Exogenous administration of S-Adenosylmethionine (SAM), a methyl donor agent, was suggested to induce cancer cell death by affecting DNA methylation pattern. In this study, we investigate the cytotoxic effect of SAM on two glioblastoma (GB) cell lines (18 and 38) in vitro. For this purpose, we treated the cells with increasing doses of SAM, and analyzed the cell viability by MTT assay, 7 days after the treatment. We found that SAM treatment induced cytotoxicity in both cell lines, but the 38 cells were more sensitive than 18 cells. This biological methyl donor was demonstrated to inhibit the mitogenic effect of growth factors in cancer cells. Here, we hypothesize that SAM induced igf-1r hypermethylation and subsequently IGF-1R downregulation, would be the cause of the cytotoxicity of the SAM treatment in GB cells. This hypothesis was encouraged by our previous results, showing that IGF-1R function is important for GB cell survival and proliferation. First, we found that in both GB cell lines expressing IGF-1R, the igf-1r was partially methylated. To our knowledge this is the first report describing the methylation status of igf-1r promoter gene in glioblastoma cells. The next set of experiments indicated that SAM treatment did not modify the igf-1r CpG island methylation status or the expression of the IGF-1R, suggesting that SAM - induced cytotoxicity is independent of igf-1r methylation in glioblastoma cell lines.

Keywords: DNA methylation,glioblastoma,Igf-1r

 
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How to cite
Ola R, D. I, Berindan I, Bălăcescu O, Bănicioiu M, Dricu A. S-Adenosylmethionine - induced cytotoxicity in glioblastoma cells does not affect the Igf-1r methylation. Rev Romana Med Lab. 2010;18(3):51-9