c-Myc and Bcl-2 Protein Expression During the Induction of Apoptosis and Differentiation in TNFα-Treated HL-60 Cells

Abstract

We examined c-Myc and Bcl-2 protein expressions during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells using a two-color flow cytometric method. We found that c-Myc protein was rapidly down-regulated in the apoptotic cells while Bcl-2 protein was expressed at relatively high levels. Concomitantly with terminal differentiation Bcl-2 protein was down-regulated in differentiating cells as well as c-Myc protein. We also showed that c-myc antisense oligonucleotides could induce apoptosis in HL-60 cells whereas bcl-2 antisense did not induce apoptosis during the early time of treatment. These results suggest that the down-regulation of c-Myc protein expression is a primary event to induce apoptosis and neither consistent expression of c-Myc protein nor rapid down-regulation of Bcl-2 protein is necessary for the initial processing of apoptosis in HL-60 cells. Furthermore, concomitant down-regulation of c-Myc and Bcl-2 is closely associated with terminal differentiation and apoptotic cell death of HL-60 cells treated with TNF alpha.

Ethanol Extract of Tripterygium wilfordii Hook. F. Induces G0/G1 Phase Arrest and Apoptosis in Human Leukemia HL-60 Cells Through c-myc and Mitochondria-Dependent Caspase Signaling Pathways

“…Regulation of the relative levels of Bcl-2 and c-Myc may play an important role in modulating the susceptibility of cells to differentiation (Li et al, 2004;Wu et al, 2002). Previous studies have demonstrated that HL-60 cells exhibited an overexpression of Bcl-2 and c-Myc proto-oncogene and that alteration of cellular oncogenes occur during the differentiation of HL-60 cells (Kumakura et al, 1996). Within myeloid lineage, Bcl-2 is over-expressed in early myeloid precursors but under-expressed or absent in matured myeloid cells and neutrophils (Gazitt et al, 2001;Blagosklonny et al, 1996).…”

“…Differentiation of HL-60 is induced into granulocytes by dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA), and into monocytic-like cells by phorbol ester (TPA) and 1,25-dihydroxy-vitamin D3 (Tsiftsoglou et al, 2003). In HL-60 cells, differentiation is induce-specific and is characterized by agents to differentiated is a marked increase in the proportion of G0/G1 cells (Yen et al, 2006), and the modulation of cyclin/CDK (Horie et al, 2004;Wang et al, 1996;Barrera et al, 2004;Pizzimenti et al, 1999;Kumakura et al, 1996).…”

Low-dose ionizing radiation effects on differentiation of HL-60 cells

“…Concomitant down-regulation of c-MYC and BCL-2 are important early events closely associated with cell growth arrest, terminal differentiation and apoptotic death in several cell types [54,55]. In leukemia cells, c-MYC expression decreases within 12 h of RA stimulation and is further down-regulated during differentiation [56].…”

Tumor necrosis factor-α enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway

“…Tumor necrosis factor-a has been shown to induce cell differentiation in several leukemic cell lines including HL-60, U937, and WEHI-3B JCS [9,[21][22][23]. Furthermore, it has been shown that the differentiation of the human leukemic cells into mature cells is enhanced by the combination of TNF-a and interleukin-4 (IL-4) [9].…”