Abstract C88: Imiquimod induces reactive oxygen species- and caspase-independent cell cycle arrest and apoptosis in MDA-MB-468 breast cancer cells
Bibliographic record
Abstract
Abstract Imiquimod is an immune modulator currently used as a topical treatment for superficial basal cell carcinoma. Recently, apoptosis-inducing activity in neoplastic cells has been attributed to imiquimod at doses over a 1000-fold lower than those used in topical applications. The present study examined the direct effect of imiquimod on MDA-MB-468 breast cancer cells. Oregon Green 488 staining of imiquimod-treated MDA-MB-468 cells indicated that imiquimod had a dose-dependent, anti-proliferative effect; cell cycle analysis indicated that arrest occurred in S phase after 72 h exposure to imiquimod. In addition, imiquimod had a time- and dose-dependent cytotoxic effect on a panel of breast cancer cells (MDA-MB-468, MDA-MB-231, MCF-7, and T47D). Double staining of imiquimod-treated MDA-MB-468 cells using Annexin-V-FLOUS and propidium iodide indicated that imiquimod caused apoptosis, while the lack of lactate dehydrogenase release confirmed the absence of necrosis. Unlike previously reported data for other neoplastic cells, imiquimod-induced apoptosis was not caspase-dependent in MDA-MB-468 cells; however, DiOC6 staining revealed destabilization of the mitochondrial membrane following imiquimod treatment. Pretreatment with reduced glutathione did not rescue MDA-MB-468 cells from imiquimod-induced apoptosis, indicating that reactive oxygen species were not required for imiquimod-induced cytotoxicity. Western blotting showed that imiquimod-treated MDA-MB-468 cells had increased cytosolic cytochrome c and PARP cleavage compared to controls, which was consistent with induction of the mitochondrial pathway of apoptosis. These data suggest that imiquimod exerts a significant caspase-independent apoptosis-promoting effect on breast cancer cells. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C88.
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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) | 0.001 | 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 | 0.001 |
| 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".