Growth-inhibition by hemin in K562 human leukemic cells is related to hemoglobin-producing activity.
To determine the mechanism of the growth inhibition associated with the induction of erythroid differentiation in K562 cells by hemin, we used two K562 subclones with different hemoglobin (Hb)-producing activity. Hemin strongly inhibited the growth of K562-L, which had a low Hb-producing activity, but not that of K562-H, which had a high Hb-producing activity. When the cell growth of K562-L was inhibited by hemin, the S phase of the cell cycle decreased and the G2/M phase increased. In contrast, hemin had no effect on the cell cycle of K562-H. Without hemin treatment, the alpha-globin mRNA level was related to the degree of Hb production in K562-L and -H but the gamma-globin mRNA level was not. With hemin treatment, there was no increase in the alpha-globin mRNA level in K562-L but there was an increase in K562-H. The difference in alpha-globin mRNA levels correlated with the Hb production in K562-L and -H induced by hemin. The levels of c-myc and c-myb mRNAs in K562-L decreased when cell growth was strongly inhibited by hemin. These findings indicate that the growth inhibition of K562 cells by hemin is due to a suppression of the progression from the G0/G1 phase to the S phase and a delay in the G2/M phase, caused by the inhibition of c-myc and c-myb transcription. It is also affected by the Hb production, reflected in alpha-globin transcription.
Sasaki
D
D
Department of Microbiology, Tohoku College of Pharmacy, Sendai, Japan.
Kosunago
S
S
Mikami
T
T
Matsumoto
T
T
Suzuki
M
M
D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D005914:Globins / Q000096:biosynthesis; D006427:Hemin / Q000494:pharmacology*; D006454:Hemoglobins / Q000096:biosynthesis*; D006801:Humans; D007942:Leukemia, Experimental / Q000378:metabolism*; D009857:Oncogenes / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D006454:Hemoglobins; D012333:RNA, Messenger; D006427:Hemin; D005914:Globins