G-CSF induces apoptosis of a human acute promyelocytic leukemia cell line,UF-1: Possible involvement of Stat3 activation and altered Bax expression

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that regulates the proliferation, differentiation and survival of cells in the granulocyti c lineage. In this study, however, we found that G-CSF or interleukin-6 (IL -6) induced UF-1, a human acute promyelocytic leukemia cell line, into apop tosis that was confirmed by morphological features and DNA fragmentation. T his rare response is demonstrated for the first time with human acute promy elocytic leukemia cell line. The apoptosis induced by G-CSF or IL-6 was not preceded by terminal differentiation characterized by morphological matura tion, capability to reduce nitroblue tetrazolium, or surface CD11b expressi on. Interestingly, Western blot analysis revealed that the stimulation of U F-1 with either G-CSF or IL-6 resulted in excessive activation of both sign al transducer and activator of transcription 3 alpha (Stat3 alpha) and Stat 3 beta. Furthermore, an additional 18 kDa Bax-related protein was expressed by the stimulation of G-CSF or IL-6, while Bcl-2 and Bcl-X proteins remain ed unchanged. These findings suggest that UF-1 may be a valuable tool in in vestigating the aberrant regulation of apoptosis, especially the Stat3 invo lvement in the mechanism of apoptosis induction.