Effects of KNK437 on heat-induced methylation of histone H3 in human oral squamous cell carcinoma cells.

Purpose: Methylation of H3 at lysine 4 (H3 Lys4) may be correlated with active gene trascription, whereas methylation of H3 at lysine 9 (H3 Lys9) may be linked to gene repression in murine cells and Schizosaccharomyces pombe.Methods: Using Western blot analysis, heat-induced changes were studied in two human oral cancer cell lines, HSC4 (thermoresistant cells) and KB (thermosensitive cells). Histone H3 changes were studied; in particular for H3-Lys4 and H3-Lys9 methylation combined with KNK437.Results: Heating of HSC4 cells at 45°C for 20 min and KB cells for 3 min gradually increased H3-Lys4 and H3-Lys9 methylation. Treatment of both cells with 100 µM KNK437 before or after heat-treatment inhibited methylation of H3-Lys4, while methylation of H3 Lys9 remained unaffected. Use of KNK437 either before or after heat treatment inhibited the expression of HSP70.Conclusions: The findings suggest that heat-induced methylation of histone H3 may be correlated with the induction of HSPs by heating.