Evaluation of the Cytotoxic Effects of the Novel Antineoplastic Agent 1,4,5-Oxathiazinane-4,4-dioxide on Triple Negative Breast Cancer Cells
| Autor: | D. Peter O’Leary, Jiang Huai Wang, H. Paul Redmond, Rolf W. Pfirrmann, Mark Corrigan, M. Jinih |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell death
Cancer Research Programmed cell death Necrosis Cell Survival Cytotoxicity Necroptosis Drug Evaluation Preclinical Antineoplastic Agents Apoptosis Triple Negative Breast Neoplasms Cell Line Tumor Triple-negative breast cancer cells Autophagy medicine Humans Cytotoxic T cell Viability assay Triple-negative breast cancer Cell Proliferation Dose-Response Relationship Drug Molecular Structure Chemistry Cancer General Medicine medicine.disease OTD Oncology Cancer research medicine.symptom Reactive oxygen species Reactive Oxygen Species |
| Zdroj: | Anticancer Research. 41:2247-2256 |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.15001 |
| Popis: | Background/aim Adjuvant therapeutic options are limited for triple negative breast cancer (TNBC). Thus, we evaluated the cytotoxic effects of the newly synthesized antineoplastic agent 1,4,5-Oxathiazinane-4,4-dioxide (OTD) on TNBC cells as a potential cancer therapeutic strategy. Materials and methods TNBC primary BT-20 and metastatic MDA-MB-231 cell lines were treated with increasing concentrations of OTD for various time periods to assess cell viability. Cell necrosis, apoptosis, necroptosis, autophagy, and ROS generation were evaluated using assay kits or specific inhibitors. Results Treatment with OTD resulted in a dose- and time-dependent cell death of TNBC BT-20 and MDA-MB-231 cells. OTD also dose-dependently arrested TNBC cell proliferation. Notably, treatment with OTD induced both necrosis and apoptosis of TNBC cells, while the pan-caspase inhibitor Z-VAD-FMK partially attenuated OTD-induced cell death. Importantly, abrogated OTD-induced cell death was observed in the presence of the ROS scavenger N-acetylcysteine (NAC), whereas enhanced OTD-induced cell death was observed after the addition of the glutathione synthesis inhibitor BSO, indicating OTD-induced killing of TNBC cells via a reactive oxygen species-dependent mechanism. Conclusion OTD is strongly cytotoxic to both primary and metastatic TNBC cells, possibly by inducing multiple cell death pathways. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|