Methionine addiction is a fundamental and general hallmark of
cancer.
Methionine addiction prevents
cancer cells, but not normal cells from proliferation under
methionine restriction (MR). Previous studies reported that MR altered the
histone methylation levels in
methionine-addicted
cancer cells. However, no study has yet compared the status of
histone methylation status, under MR, between
cancer cells and normal cells. In the present study, we compared the
histone methylation status between
cancer cells and normal fibroblasts of
H3K4me3 and H3K9me3, using recombinant
methioninase (rMETase) to effect MR. Human lung and
colon cancer cell lines and human normal foreskin fibroblasts were cultured in control medium or medium with rMETase. The viability of foreskin fibroblasts was approximately 10 times more resistant to rMETase than the
cancer cells in vitro. Proliferation only of the
cancer cells ceased under MR. The
histone methylation status of
H3K4me3 and H3K9me3 under MR was evaluated by immunoblotting. The levels of the
H3K4me3 and H3K9me3 were strongly decreased by MR in the
cancer cells. In contrast, the levels of
H3K4me3 and H3K9me3 were not altered by MR in normal fibroblasts. The present results suggest that
histone methylation status of
H3K4me3 and H3K9me3 under MR was unstable in
cancer cells but stable in normal cells and the instability of
histone methylation status under MR may determine the high
methionine dependency of
cancer cells to survive and proliferate.