title: Growth-inhibition by hemin in K562 human leukemic cells is related to hemoglobin-producing activity.
abstract: 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.
authors.affiliation: Department of Microbiology, Tohoku College of Pharmacy, Sendai, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Kosunago
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
mesh_terms: 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
chemical_list: D006454:Hemoglobins; D012333:RNA, Messenger; D006427:Hemin; D005914:Globins