Experimental Study On VPA-induced Glutathione-redox Imbalance, Apoptosis And Reversal Of Drug Resistance In Hematopoietic Malignant Cells

Background Despite recent advances in the treatment of childhood cancers, leukemias remain the primary cause of cancer-related mortality among children under 12 in China.. Roughly 30% of the patients relapsed after remission and died sooner or later. Drug resistance is a major obstacle to successful treatment of leukemia. Some children shows resistance to chemotherapetutic agents, say dexamethasone, at the onset of the dieases, and some more, develop drug resistance during the course of intensive chemotherapy. Therefore, there is a need for novel antileuklemia agents, especially those that are effective for lekemias resistant to existing chemotherapeutic agents.Anti-tumoral effects of Histone acetylation play a key role in the regulation of transcription by modulating chromatin structure. In general, histone acetylation is associated with activation of transcription, whereas histone . deacetylation is associated with repression of transcription. It has been established that many malignancies, particularly leukemia, are associated with aberrant recruitment of histone deacetylases (HDACs) or with mutations in histone acetyl transferases. So application of Histone deacetylases inhibitors to leukemia patients seems plausible. In fact, Histone deacetylase inhibitors...