SODIUM BUTYRATE ENHANCES THE ANTIPROLIFERATIVE EFFECT OF HIGH CONCENTRATIONS OF ACTINOMYCIN D

In the present article we have studied the combined effect of actinomycin D (AMD) with HDI sodium butyrate (NaBut) on proliferation of transformed cells. It has been shown that NaBut increased the cytotoxic effect of low concentrations of AMD (8 nM). However, the viability of the cells transformed with E1A + Ras was slightly increased under the joint action of high concentrations of AMD and NaBut. Simultaneous action of NaBut and low concentration of AMD sharply reduced the clonogenic survival of transformed cells, in parallel with increased apoptotic cell death.The study of the mechanisms of cell death induced by the combined action of NaBut and low concentrations of AMD showed that the joint treatment resulted in activation of proapoptotic transcription factor p53 and the suppression of the activity of anti-apoptotic factor NF-kB. Thus, NaBut increased cytotoxic effect of low concentrations of AMD in oncogene-transformed cells under the joint action, increasing their apoptotic death. These results can be used in the selection of the correct dosage of drugs for the effective combined anti-cancer therapy using HDIs and AMD.