Abstract 4217: The anti-malarial compound artesunate induces reactive oxygen species-dependent killing of breast cancer cells
Bibliographic record
Abstract
Abstract Introduction: Artesunate is a semi-synthetic derivative of artemisinin, a natural compound from the herb Artemisia annua L. Artemisinin has been used in traditional Chinese medicine while artesunate has recently been used as an anti-malarial drug. Artesunate is also cytotoxic to human cancer cells. Since the use of artesunate as an anti-malarial agent is associated with few adverse effects, artesunate may represent a less toxic alternative to conventional chemotherapy. This study investigates the cytotoxic effect of artesunate on breast cancer cell lines and the mechanism(s) underlying its activity. Methods and Results: Artesunate exhibited a time- and dose-dependent cytotoxic effect on all breast carcinoma cell lines examined (MCF-7, T47D, SK-BR-3, MDA-MB-231, MDA-MB-468). Further examination of MDA-MB-468 cells using Oregon Green-488 and Annexin-V-FLUOS/propidium iodide staining indicated that artesunate had an anti-proliferative effect that was associated with apoptosis induction. Cell cycle arrest occurred in the G2 phase, and was evident as early as 24h after artesunate treatment. Artesunate-induced apoptosis was low in normal fibroblasts at concentrations cytotoxic to breast cancer cells, although fibroblast proliferation was inhibited. DiOC6 staining revealed dose-dependent destabilization of the mitochondrial membrane in artesunate-treated MDA-MB-468 cells. Artesunate-treated MDA-MB-468 cells also displayed cytosolic cytochrome c and PARP cleavage, as demonstrated by Western blotting, which was consistent with apoptosis induction. Pretreatment with reduced glutathione rescued MDA-MB-468 cells from artesunate-induced apoptosis, indicating that reactive oxygen species (ROS) mediate artesunate-induced cytotoxicity. In addition, MDA-MB-468 cells that were pretreated with holotransferrin showed increased killing by artesunate, suggesting that iron promotes artesunate-mediated apoptosis. Induction of the endoplasmic reticulum stress pathway in artesunate-treated cells was demonstrated by Western blotting, suggesting involvement of this apoptosis-inducing pathway in artesunate-mediated cytotoxicity. Conclusions: These data show that artesunate causes reactive oxygen species-dependent induction of apoptosis in breast cancer cells and therefore warrants further investigation as a possible treatment for breast cancer. Supported by NSERC and the Canadian Breast Cancer Foundation-Atlantic Region Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4217. doi:10.1158/1538-7445.AM2011-4217
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.004 | 0.001 |
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".