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APOPTOSIS DURING IRON CHELATOR‐INDUCED DIFFERENTIATION IN F9 EMBRYONAL CARCINOMA CELLS
Author(s) -
Tanaka Tetsuya,
Satoh Takatomo,
Onozawa Yoshiko,
Kohroki Junya,
Itoh Norio,
Ishidate Motoi,
Muto Norio,
Tanaka Keiichi
Publication year - 1999
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.1999.0407
Subject(s) - apoptosis , sodium butyrate , cell cycle , programmed cell death , retinoic acid , cellular differentiation , microbiology and biotechnology , cell growth , dna fragmentation , cell cycle checkpoint , fragmentation (computing) , viability assay , deferoxamine , cell culture , cell , chemistry , differentiation therapy , biology , biochemistry , ecology , gene , genetics , acute promyelocytic leukemia
We have previously demonstrated that three potent iron chelators, hinokitiol, dithizone and deferoxamine, induce differentiation of F9 embryonal carcinoma cells, as do other well‐known morphogens such as retinoic acid (RA) and sodium butyrate (NaB). In this study, we compared the patterns of cell proliferation, cell death and cell cycle arrest during the process of differentiation induced by these five agents. When F9 cells were cultured with the agents at their individual differentiation‐inducing concentrations, cell proliferation was rapidly inhibited by treatment with the iron chelators and NaB. In contrast, RA did not influence the rate of increase of cell number at the concentration of 1 μ m . The three chelators also caused a marked reduction in cell viability, and the treated cells exhibited internucleosomal DNA fragmentation, whereas cells treated with NaB showed no apoptotic characteristics. RA induced apoptosis weakly at 1μ m and strongly at higher concentrations. In addition, all the iron chelators hindered cell cycle progression, resulting in an arrest at the G1‐S interface or S phase. The phenomena observed in chelator‐treated cells were considerably different from those in RA‐ or NaB‐treated cells. It is concluded that the three iron chelators cause both severe apoptotic cell death and cell cycle arrest of proliferating F9 cells via cellular iron deprivation, and that this apoptotic change may be independent of the process of differentiation.