Effects of KNK437 on heat-induced methylation of histone H3 in human oral squamous cell carcinoma cells.
OBJECTIVE
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 degrees C for 20 min and KB cells for 3 min gradually increased H3-Lys4 and H3-Lys9 methylation. Treatment of both cells with 100 microM 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.
Matsuda
Keiji
K
Division of Radiological Technology, Graduate School of Health Science, Okayama University, Okayama, Japan.
Nakagawa
Shin-Ya
SY
Nakano
Tomoya
T
Asaumi
Jun-Ichi
J
Jagetia
Ganesh Chandra
GC
Kawasaki
Shoji
S
D001559:Benzhydryl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006657:Histones / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D007624:KB Cells; D008745:Methylation; D009062:Mouth Neoplasms / Q000628:therapy*; D018307:Neoplasms, Squamous Cell / Q000628:therapy*; D011760:Pyrrolidinones / Q000494:pharmacology*
D001559:Benzhydryl Compounds; D006360:Heat-Shock Proteins; D006657:Histones; C410027:KNK 437; D011760:Pyrrolidinones