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Cell Growth & Differentiation Vol. 13, 19-26, January 2002
© 2002 American Association for Cancer Research

Control of Differentiation and Apoptosis of Human Myeloid Leukemia Cells by Cytokinins and Cytokinin Nucleosides, Plant Redifferentiation-inducing Hormones1

Yuki Ishii, Yuko Hori, Shingo Sakai and Yoshio Honma2

Saitama Cancer Center Research Institute, Saitama 362-0806 [Y. I., Y. Hor., Y. Hon.], and Institute of Biological Science, Tsukuba University, Tsukuba, Ibaraki 305-8572 [Y. I., Y. Hor., S. S.], Japan

We examined the effects of various adenine analogues on the growth and differentiation of human myeloid leukemia HL-60 cells. Some of these analogues inhibit growth and induce nitroblue tetrazolium reducing activity in HL-60 cells. Cytokinins such as kinetin, isopentenyladenine, and benzyladenine were very effective in inducing nitroblue tetrazolium reduction and morphological changes in the cells into mature granulocytes. On the other hand, cytokinin ribosides such as kinetin riboside, isopentenyladenosine, and benzylaminopurine riboside were the most potent for growth inhibition and apoptosis. Cytokinin ribosides greatly reduced the intracellular ATP content and disturbed the mitochondrial membrane potential and the accumulation of reactive oxygen species, whereas cytokinins did not. When the cells were incubated with cytokinin ribosides in the presence of O2- scavenger, antioxidant or caspase inhibitor, apoptosis was significantly reduced and differentiation was greatly enhanced. These results suggest that both cytokinins and cytokinin ribosides can induce granulocytic differentiation of HL-60 cells, but cytokinin ribosides also induce apoptosis prior to the differentiation process.




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Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2002 by the American Association of Cancer Research.