Abstract 2262: Anti-proliferative and cytotoxic activities of the anti-malarial compound artesunate for breast and ovarian cancer cell lines.
Bibliographic record
Abstract
Abstract Introduction: In women, breast cancer is the most prevalent cancer diagnosis while ovarian cancer represents the most lethal gynecological neoplasm. Together, these cancer types place a huge burden on society, comprising 20% of all estimated cancer deaths in the USA for 2012. The high incidence and mortality rates of these cancer types, in addition to the emergence of multi-drug resistant variants, highlights the need to develop novel therapeutic agents with greater efficacy. Artesunate (ART) is a semi-synthetic derivative of artemisinin, a natural compound derived from the Chinese herb Artemisia annua L. ART is an antimalarial agent that also possesses potent anticancer activity. Since the use of ART as an antimalarial agent is associated with few adverse effects, ART may represent a less toxic alternative to conventional chemotherapy. This study investigates the cytotoxic effects of ART on breast and ovarian cancer cell lines and the mechanisms underlying its activity. Methods & Results: ART exhibited a dose- and time-dependent effect on a panel of breast and ovarian cancer cell lines. Anticancer activity was also observed in 3-D cultures of both cancer cell types. Oregon Green 488 and propidium iodide (PI) staining of cancer cells revealed that ART strongly inhibited cancer cell proliferation, arresting cells in the G1 or G2 phases of the cell cycle. ART-mediated G2 arrest was dependent on reactive oxygen species (ROS), as in the presence of an antioxidant all cell lines arrested in G1. ART's antiproliferative effect was due in part to its ability to modulate the expression of cell cycle regulatory proteins including cyclin D3, p21, CDK4 and CDC25C. Annexin V/PI staining of ART-treated cancer cells revealed that ART induced ROS-dependent apoptosis in both breast and ovarian cancer cell lines. Pretreatment of cancer cells with a pan-caspase inhibitor decreased but did not eliminate ART-induced cytotoxicity, suggesting that caspase-dependent apoptosis is one of several pathways involved in ART-mediated killing of cancer cells. ART caused ROS-dependent DNA damage indicated by the presence of γH2AX, which implicates the DNA damage pathway in ART-induced cancer cell death. Annexin V/PI staining of ART-treated normal dermal fibroblasts and human mammary epithelial cells demonstrated that ART had limited cytotoxicity for normal cells at doses that were toxic to cancer cells, highlighting an increased sensitivity of cancer cells to ART treatment. Conclusions: These data show that ART has a potent antiproliferative and cytotoxic effect on both breast and ovarian cancer cells with limited cytotoxicity for normal cells. ART's specific cytotoxic activity and excellent safety record in malaria patients make it a worthy candidate for further investigation as a possible treatment for breast and ovarian cancer. Supported by NSERC and the CBCF-Atlantic Region Citation Format: Anna L. Greenshields, David Hoskin. Anti-proliferative and cytotoxic activities of the anti-malarial compound artesunate for breast and ovarian cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2262. doi:10.1158/1538-7445.AM2013-2262
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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 | 0.001 |
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".