Abstract #850: Cytotoxic activity of two pleurocidin-like cationic antimicrobial peptides against human breast cancer cells
Bibliographic record
Abstract
Cationic antimicrobial peptides are small peptides that constitute an important defense against microbial pathogens and, in some cases, also exhibit potent cytotoxic activity against cancer cells. Atlantic pleuronectid flatfish are a particularly rich source of cationic antimicrobial peptides, including NRC-03 and NRC-07, which are pleurocidin-like peptides derived from winter and yellowtail flounder, respectively. The purpose of this investigation was to evaluate the potential of NRC-03 and NRC-07 as novel cytotoxic agents for the treatment of breast cancer. Colorimetric MTT and LDH-release assays showed that NRC-03 and NRC-07 rapidly killed MDA-MB-231, MDA-MB-468, MCF-7 and T47D human breast cancer cells in a time- and dose-dependent manner. Additionally, NRC-03 and NRC-07 were cytotoxic towards cisplatin-resistant human ovarian cancer cell lines. Colorimetric hemolytic assays revealed that neither NRC-03 nor NRC-07 possessed hemolytic activity. Human fibroblasts and umbilical vein endothelial cells were not harmed by NRC-03 or NRC-07; however, high concentrations of NRC-03 and NRC-07 were lytic for human T cells and mammary epithelial cells, suggesting that both peptides require modification to enhance breast cancer cell selectivity. Fluorescent microscopy revealed that fluorochrome-labeled NRC-03 and NRC-07 rapidly bound to the surface of breast cancer cells, but not human dermal fibroblasts, suggesting that peptide binding was required for cell death. Propidium iodide staining, as well as scanning electron microscopy, showed that NRC-03 and NRC-07 rapidly caused pore formation in the cellular membrane of breast cancer cells, suggesting that cell death was mediated by membrane lysis. However, flow cytometric analysis of dihydroethidium- or DiOC 6 -stained breast cancer cells revealed that NRC-03- and NRC-07-mediated cytotoxicity was also associated with reactive oxygen species production and mitochondrial membrane destabilization, respectively. Nevertheless, the pan-caspase inhibitor BOC-D-FMK did not prevent NRC-03- and NRC-07-induced cytotoxicity, supporting the hypothesis that NRC-03 and NRC-07 act primarily through a membrane-lytic mechanism. We conclude that NRC-03 and NRC-07 warrant further investigation as novel therapeutic agents for the treatment of breast cancer. Supported by Natural Science and Engineering Research Council of Canada, the Cancer Research Training Program, and the Canadian Breast Cancer Foundation - Atlantic Region Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 850.
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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) | 0.004 | 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".