Induction of apoptosis and inhibition of cell growth are independent responses to interferon-alpha in hematopoietic cell lines.
IFNs are capable of modulating a variety of cellular responses, including cell growth and apoptosis. The prospective connections between these two biological responses are not fully understood, and the molecular mechanisms underlying the effects of IFNs on these processes are not completely defined. We have investigated the relationship between IFN-alpha-induced apoptosis and cell cycle arrest in three hematopoietic cell lines, Daudi, U-266, and H9. It was found that IFN-alpha was a rapid and potent inducer of apoptosis in H9 and U-266 cells, whereas IFN-alpha-induced cell cycle arrest in Daudi cells is not associated with the onset of apoptosis. In H9 cells, apoptosis occurs without a preceding cell cycle block, whereas in U-266 cells, apoptosis occurs subsequent to G1 arrest. Cell cycle arrest per se, induced by serum starvation or treatment with aphidicolin, had only minor effects on the viability of these cell lines and did not abrogate the apoptosis-inducing capacity of IFN-alpha. Additionally, IFN-alpha-induced apoptosis occurred in cells from all cell cycle phases. Thus, we conclude that IFN-alpha-induced apoptosis seems to occur independent of cell growth inhibition. There were no changes in Bcl-2 or Bax protein levels that could account for the apoptosis-inducing effects of IFN-alpha in these cell lines. Moreover, examination of p53 status suggests that IFN-alpha-induced apoptosis in the U-266 and H9 cell lines occurs through a p53-independent pathway.
Sangfelt
O
O
Department of Oncology/Pathology, Karolinska Hospital and Institute, Stockholm, Sweden.
Erickson
S
S
Castro
J
J
Heiden
T
T
Einhorn
S
S
Grandér
D
D
D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004247:DNA; D001973:Bromodeoxyuridine