Biological effects of a relatively low concentration of XXXX in K562 cells: alterations of the cell cycle, erythroid-differentiation, and apoptosis.

@entity1 @entity589 @entity517 @entity1778 @entity1178 @entity9864 @entity1860 @entity995
Therapeutic strategies for @entity1778 are directed to induction of differentiation and apoptosis as well as growth inhibition. One of the key antileukemic agents, @entity9864 (ara C), is clinically applied according to these therapeutic aims. However, the molecular effects of 0.1 microg/ml of ara C, a concentration that corresponds to the serum level in @entity1778 @entity1 on a conventional dose of ara C, have not been well disclosed. Here, we addressed these issues using K562 cells which derived from a blastic crisis of @entity1860 . DNA synthesis of treated cells was suppressed from 1-6 h. But, it recovered at 12 h and no further inhibition was observed. The number of cells was not decreased but DNA fragmentation was observed at 72 h. The number of erythroid-differentiated cells also increased to 30% at 72 h. Along with treatment, no marked alteration of mRNAs for cell cycle-regulating genes was found and the @entity995 gene product remained hyperphosphorylated throughout treatment. The expression of mRNAs for apoptosis-regulating genes also remained unchanged, except for slight down-regulation of @entity589 . @entity517 protein was not found later than 48 h, and Max mRNA was downregulated. @entity1178 was immediately induced, followed by the fluctuated expression level along with treatment. These findings suggest that the 0.1 microg/ml ara C changed the proliferation, differentiation and death of K562 cells in a biphasic manner. In the early phase, DNA synthesis was inhibited without altering the expression of cell cycle regulating-genes. In the latter phase, cell death and erythroid- differentiation occurred in accordance with the down-regulation of @entity517 .
