TY - JOUR
T1 - Evidence against a Direct Role for the Induction of c-jun Expression in the Mediation of Drug-induced Apoptosis in Human Acute Leukemia Cells
AU - Bullock, Gloria
AU - Ray, Swapan
AU - Reed, John
AU - Miyashita, Toshiyuki
AU - Ibrado, Ana Maria
AU - Huang, Yue
AU - Bhalla, Kapil
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1995/5/1
Y1 - 1995/5/1
N2 - Previous reports have demonstrated that a variety of anticancer drugs, e.g., 1-β-D-arabinofuranosylcytosine (ara-C), mitoxantrone, etoposide, camptothecin, and cisplatin, induce the expression of c-jun oncogene in leukemic cells prior to producing internucleosomal DNA fragmentation and the morphological features of apoptosis. This has led to the impression that the induction of c-jun expression may be directly involved in the molecular signaling of the final common pathway of programmed cell death or apoptosis. In the present study, we examined the role of c-jun expression in three different settings of anticancer drug-induced apoptosis in human leukemic cells. First, exposure of human myeloid leukemia HL-60 cells to high-dose ara-C for 4 h produced internucleosomal DNA fragmentation preceded by c-jun induction. However, pretreatment of HL-60 cells with staurosporine, a protein kinase C inhibitor, repressed c-jun yet enhanced DNA fragmentation and apoptosis due to ara-C. Second, in human pre-B leukemia 697/BCL-2 cells which are transfected with the cDNA of the BCL-2 oncogene and overexpress p26BCGL-2, although ara-C or miterantrone treatment caused greater c-jun induction than in the 697/neo cells, significantly reduced endonuclolytic DNA fragentation and apoptosis was observed in 697/BCL-2 cells. Finally, taxol-induced internucleosomal DNA fragmentation and morphological features of apoptosis in HL-60 cells were not associated with the induction of c-jun expression, These lines of evidence indicate that the induction of c-jun expression may not have a direct role in the molecular signaling of anticancer drug-induced apoptosis, and that the anticancer drug-induced apoptosis can occur by a mechanism that does not involve the induction of c-jun expression.
AB - Previous reports have demonstrated that a variety of anticancer drugs, e.g., 1-β-D-arabinofuranosylcytosine (ara-C), mitoxantrone, etoposide, camptothecin, and cisplatin, induce the expression of c-jun oncogene in leukemic cells prior to producing internucleosomal DNA fragmentation and the morphological features of apoptosis. This has led to the impression that the induction of c-jun expression may be directly involved in the molecular signaling of the final common pathway of programmed cell death or apoptosis. In the present study, we examined the role of c-jun expression in three different settings of anticancer drug-induced apoptosis in human leukemic cells. First, exposure of human myeloid leukemia HL-60 cells to high-dose ara-C for 4 h produced internucleosomal DNA fragmentation preceded by c-jun induction. However, pretreatment of HL-60 cells with staurosporine, a protein kinase C inhibitor, repressed c-jun yet enhanced DNA fragmentation and apoptosis due to ara-C. Second, in human pre-B leukemia 697/BCL-2 cells which are transfected with the cDNA of the BCL-2 oncogene and overexpress p26BCGL-2, although ara-C or miterantrone treatment caused greater c-jun induction than in the 697/neo cells, significantly reduced endonuclolytic DNA fragentation and apoptosis was observed in 697/BCL-2 cells. Finally, taxol-induced internucleosomal DNA fragmentation and morphological features of apoptosis in HL-60 cells were not associated with the induction of c-jun expression, These lines of evidence indicate that the induction of c-jun expression may not have a direct role in the molecular signaling of anticancer drug-induced apoptosis, and that the anticancer drug-induced apoptosis can occur by a mechanism that does not involve the induction of c-jun expression.
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M3 - Article
C2 - 9816016
AN - SCOPUS:0029079447
SN - 1078-0432
VL - 1
SP - 559
EP - 564
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -