A Role for Resveratrol and Curcumine in Sensitization of Glioblastoma Cells to Genotoxic Stress Induced by Alkylating Chemotherapeutics

摘要

Curcumine and resveratrol are phytochemicals for which anticancer, anti-oxi-dant and anti-inflammatory activity have been reported. Resveratrol is a phy-toalexin which is found in the skin of red grapes, curcumine is a polyphenol, responsible for the yellow colour of turmeric. Both agents are currently dis-cussed as potential drug modifiers, either protecting or sensitizing cells against genotoxic stress. However, the impact of these compounds on chemotherapy has not been elucidated in great detail. To clarify this, we analyzed the influence of curcumine and resveratrol on DNA repair and sensitivity to cytostatic drugs. To this end we utilized glioblastoma cell lines differing in their p53 and MGMT status. All these cell lines were similarly sensitive to curcumine and resveratrol. Whereas no influence of curcumine and resveratrol on base excision repair was detected, we could show an effect on the DNA repair enzyme MGMT. Treat-ment with curcumine and resveratrol induced a down-regulation of MGMT on the level of mRNA, protein and activity. In addition, curcumine and resveratrol were able to sensitize gliobla stoma cells to the chemotherapeutical drugs ACNU and temozolomide. Since this sensitization is observed also in MGMT deficient cells, the inhibitory effect of curcumine and resveratrol on MGMT activity can-not be the only reason for the observed sensitization. In MGMT deficient cells, additional mechanisms appear to be activated by curcumine and resveratrol that sensitize cells to anticancer drugs. This issue is in the focus of current in-vestigations.