Abstract 1014: Repurposing the anti-rheumatic gold compound auranofin for high-grade serous ovarian cancer therapy
Bibliographic record
Abstract
Abstract Auranofin (AF) is a gold compound approved in 1985 as a main treatment against rheumatoid arthritis. However, as new anti-rheumatoid agents displaced the use of AF, there have been studies aiming to repurpose the drug to treat other diseases, including cancer. In this study, we investigated the potentiality of AF to impair the growth of high-grade serous ovarian cancer (HGSOC) cells regardless of platinum (CDDP) sensitivity. Preliminary studies utilizing a colorimetric proliferation assay revealed that HGSOC cells that are clinically sensitive (PEO1) or resistant (PEO4) to CDDP-based chemotherapy are both equally sensitive to the growth inhibition induced by AF. The resistant factor estimated for AF-defined as the ratio between IC50 values calculated for the resistant cells and for the sensitive ones—was close to one, suggesting that CDDP-resistant PEO4 cells are equally sensitive to AF than CDDP-sensitive PEO1 cells. As expected, the resistant factor for CDDP was 12-fold higher in PEO4 compared to PEO1. The toxicity of AF against HGSOC cells was further studied exposing PEO1 to various concentrations of AF and assessing cell number, cell viability, and cell cycle traverse after 72 h. Results showed that AF, in a dose-dependent manner, blocked cell proliferation and caused accumulation of cells with hypo-diploid DNA content, suggesting that AF-induced cytotoxicity was associated not only with inhibition of cell proliferation but also with cell death likely driven via apoptosis. We further studied the long-term or residual toxicity of AF by exposing PEO1 cells that were alive, after 72 h treatment with AF, to a clonogenic survival assay. The results clearly demonstrated that even if not dying within 72 h, the cells were affected in a manner not compatible with long-term cell cycle progression as demonstrated by the formation of ‘abortive' colonies (i.e. colonies with few cells that show abnormal phenotypes). Finally, as AF is a pro-oxidant agent, we evaluated whether AF-induced cell death was mediated by oxidative stress by incubating PEO1 cells with AF in the presence or absence of the anti-oxidant N-acetyl-cysteine (NAC). PEO1 cells treated with AF and NAC showed no decrease in cell viability and cell number in comparison to PEO1 cells treated with AF alone. This data reveals that AF most likely induces cell death in a reactive oxygen species (ROS)-dependent manner. In conclusion, our results suggest that AF can equally impair the growth of CDDP-sensitive or -resistant HGSOC cells, and that its toxicity is likely mediated by oxidative stress. Citation Format: Farah H. Abdalbari, Alicia A. Goyeneche, Elvis Martinez-Jaramillo, Siham Sabri, Carlos M. Telleria. Repurposing the anti-rheumatic gold compound auranofin for high-grade serous ovarian cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1014.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".