The Lipoic acid/pallacium complex, DNA reductase, appears to be an effective anti-glioblastoma agent in clinical preliminary studies. The present experiments were aimed to elucidating DNA reductase's effects on CNS cells still undergoing neurogenesis. We studied the AP31 hippocampal progenitor cell line and 3T3 fibroblasts. The cells were cultured in DMEM/F12 supplemented with N2 and FGF (20ng/ml). Within 18 hours there was a significant decrease in the number of progenitor cells on poly-L-ornithine (PORN)/lamine coated plates exposed to DNA reductase (8µM), however 3T3 cells, on plastic, were unaffected by even the highest tested concentrations. Plating of 3T3 cells on coverslips further augments the effects on DNA reductase (40µM). Cervical carcinoma cells (HeLa) have been shown to have this same sensitivity to this glass substrate. Low quality glass, such as coverslip, is highly charged due to the presence of heavily charged silicates. Poly-L-ornithine promotes cell attachment by positively charging the surface Therefore, our results suggest that highly charged matrices (e.g. plastic, PORN), normally seen in growth and in tumor formation, facilitate the effects of DNA reductase, while more neutral surfaces (e.g. plastic) appear protective. (Supported by Garnett McKeen Laboratories Inc.)
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