Camptothecin- and etoposide-induced apoptosis in human leukemia cells is independent of cell death receptor-3 and -4 aggregation but accelerates tumor necrosis factor–related apoptosis-inducing ligand–mediated cell death
Bibliographic record
Abstract
During camptothecin- and etoposide (VP-16)-induced apoptosis in HL-60 cells, the expression level of cell death receptor-3 (DR3), cell death receptor-4 (DR4), and FAS remained mostly unchanged, whereas the expression of silencers of death domain (SODD) and FLICE inhibitory proteins, inhibitors of the cell death receptor signaling pathways, decreased substantially. By indirect immunofluorescence and immunoperoxidase imaging and with gel filtration column chromatography, we observed rapid aggregation at the cell surface and the appearance of high molecular weight protein complexes primarily involving DR3, and DR3 and DR4 after camptothecin and VP-16 treatment, respectively. Both drugs failed to rapidly promote FAS aggregation in these cells. The high expression level of SODD or of dominant negative forms of FADD (FADD-DN) and DAP3 (DAP3-DN), or of NH2-terminal deletion mutant of TRADD (TRADD-ND) achieved by transient transfection experiments, did not impair the kinetics of apoptosis after camptothecin and VP-16 treatment in HL-60 and U937 cells. Taken together, these observations suggested that camptothecin and VP-16 induced rapid aggregation of DR4 and DR3, but paradoxically, the importance of these events in signaling apoptosis is uncertain, because the kinetics of apoptosis were unaffected, even in the presence of a high expression level of SODD, FADD-DN, TRADD-ND, and DAP3-DN. However, camptothecin or VP-16 treatment in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) substantially accelerated kinetics of apoptosis than treatment with camptothecin, VP-16, or TRAIL alone. In contrast, cotreatment of camptothecin or VP-16 with TWEAK or TL1A did not facilitate apoptosis in HL60 cells. These findings suggest that DR4 aggregation mediated by camptothecin or VP-16 could represent a mean that accelerates TRAIL-induced apoptosis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".