The effect and comparison of sodium butyrate and trichostatin A on the differentiation of K562

AIM To analyse the mechanisms of sodium butyrate action on K562 cell differentiation and to compare them with those of trichostatin A. METHODS K562 cells were grown in the absence or presence of sodium butyrate or trichostatin A. The percentage of viable cells was determined by trypan blue exclusion. Differentiation was determined by nitro blue tetrazolium (NBT) reduction and analysed cell surface adhesion molecules by FACS. Cell cycle distribution was studied after DNA staining by propidium iodide. Cell cycle regulatory proteins were studied by Western Blot and reverse transcription polymerase chain reaction. RESULTS Sodiun butyrate blocked cells mainly in the G 0/G 1 phase of the cell cycle, whereas trichostatin A was inhibitory in G 2 phases. Sodium butyrate inhibited the mRNA expression of cyclinD1 without affecting its protein expression and stimulated the protein expression of cyclinD3 without affecting its mRNA expression. Trichostatin A showed similar effects on cyclinD1 and D3. Sodium butyrate and trichostatin A stimulated p21 expression both at the mRNA and protein levels. CONCLUSION The sodium butyrate and trichostatin A effect on cell differentiation may be linked to its ability to induce expression of cyclinD3 and p21 protein. Our observations support the claim for the therapeutic potential of sodium butyrate and trichostatin A in the treatment of chronic myelocytic leukemia.