Expression of Bcl-2 in human epithelial tumor (HeLa) cells enhances clonogenic survival following exposure to 5-fluoro-2′-deoxyuridine or staurosporine, but not following exposure to etoposide or doxorubicin

Abstract

These results indicate that Bcl-2 enhances clonogenic survival of human epithelial tumor cells in an agent-specific fashion, which may be determined by the initial cytotoxic lesion induced by a particular drug.

Mitotic Cell Death by Chromosome Fragmentation

“…Bcl-2 overexpression inhibits mitochondrial pore opening, cytochrome c release, and subsequent apoptosis (37,38). Bcl-2 overexpression was shown not to alter the frequency of chromosome fragmentation when it was induced by drug treatment of mitotic cells, despite the repression of caspase-3 expression and activation detectable in the Bcl-2-overexpressing cells compared with cells expressing an empty neo vector only.…”

“…Bcl-2 is an antiapoptotic protein that is commonly overexpressed in tumors (37,38). Bcl-2 overexpression inhibits mitochondrial pore opening, cytochrome c release, and subsequent apoptosis (37,38).…”

Inhibition of Protein Kinase Cα Enhances Anticancer Agent-Induced Loss of Anchorage-Independent Growth Regardless of Protection against Apoptosis by Bcl-2

“…In our hands, Bcl-2 overexpression was unable to protect against loss of anchorage-independent growth induced by doxorubicin or etoposide. Similar lack of long-term protection by Bcl-2 has been described for doxorubicin and etoposide in HeLa cells based on a monolayer culture clonogenicity assay (Lock and Stribinskiene, 1996;Elliott et al, 1998). Moreover, in leukemic cells Bcl-2 and Bcl-x L were unable to prevent loss of colony formation in soft agar upon exposure to Ara-C or paclitaxel, respectively, whereas apoptosis was inhibited (Wang et al, 1999;Tang et al, 2000).…”

Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells

“…30,31 Stable overexpression of Bcl-2 in these cells (clone B-5) has been shown to confer resistance to drug-induced apoptosis compared to cells transfected with empty vector alone (clone S-1). 30,31 HeLa S-1 and B-5 cells were exposed either to STP or to etoposide and subcellular fractions prepared as described above for HL-60 cells. In non-treated S-1 and B-5 cells 480% of Bax was cytosolic while almost 100% of Bcl-2 localized to membrane fractions in B-5 cells (Figures 3 and 5).…”

“…The transfection, selection and growth conditions used for both control vector-transfected (S-1) and stable Bcl-2-expressing (B-5) HeLa clones used in this study have been described previously. 30,31 Concentrated stocks of STP and etoposide were stored in DMSO at 7208C and diluted immediately prior to use. Cells were exposed continuously to 1 mM STP, or to etoposide (25 mM, 4 h) following which they were washed twice with 378C PBS and incubated in drug-free medium for the appropriate timepoints.…”