Abstract 1621: Short-time exposure to high concentrations of sunitinib causes tumor cell death
| Autor: | Henk L. Dekker, Henk M.W. Verheul, Mariette Labots, Jens Voortman, Maria Rovithi, Kristy J. Gotink, Dennis Poel, Henk J. Broxterman |
|---|---|
| Přispěvatelé: | Internal medicine, CCA - Imaging and biomarkers, CCA - Treatment and quality of life, Medical oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Programmed cell death medicine.diagnostic_test business.industry Sunitinib Cancer Pharmacology urologic and male genital diseases medicine.disease female genital diseases and pregnancy complications Flow cytometry chemistry.chemical_compound Oncology chemistry Apoptosis Cancer cell Medicine Cytotoxic T cell Propidium iodide business medicine.drug |
| Zdroj: | Cancer Research. American Association for Cancer Research Inc. Voortman, J 2013, ' Abstract 1621: Short-time exposure to high concentrations of sunitinib causes tumor cell death. ', Cancer Research . https://doi.org/10.1158/1538-7445.AM2013-1621 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Background: Sunitinib, although initially developed as an antiangiogenic agent, has been shown to exert direct anti-tumor effects. Previously we demonstrated that sunitinib inhibits proliferation of various tumor cell lines in a dose-dependent manner. We here studied whether short exposure to high peak concentrations of sunitinib would induce tumor cell death. Methods: 786-O renal cancer cells were incubated with increasing concentrations of sunitinib (5, 10 and 20 μM) for various time intervals (1 hour, 3, 6, 9, 24, 48, 72 hours). At prespecified time points, sunitinib was removed and cells were subsequently allowed to grow in drug-free culture medium. Viability of these cells one week after short time sunitinib exposure and sensitivity of recovered cells after repetitive treatment with high sunitinib concentrations were determined by MTT assays. Flow cytometry with Propidium Iodide staining was employed to determine apoptosis. Results: Short-time exposure to high concentrations of sunitinib significantly induced cell death. Exposure to 20 μM of sunitinib for 9 hours provoked cell death in a manner identical to the prolonged exposure of 24, 48 or 72 hours. Flow cytometry confirmed the significant increase in cell death (60%) after 9-hour treatment with 20 μM sunitinib, compared to the untreated control (2%). Tumor cells that were repetitively treated with high concentrations of sunitinib retain their sensitivity to the drug identical to its parental cell line. Analysis of the key signaling pathways involved in sunitinib-induced cell death is ongoing. Conclusion: We here report that repetitive short-time exposure to high concentration sunitinib causes cell death without inducing resistance. Interestingly, single-dose sunitinib up to 300 mg was previously reported to be well tolerated by patients. Based on these findings, administration of high dose intermittent sunitinib may result in cytotoxic antitumor activity irrespective of angiogenesis inhibition. A phase I trial to test this hypothesis in patients with cancer will start shortly. Citation Format: Maria Rovithi, Dennis Poel, Jens Voortman, Mariette Labots, Henk Dekker, Kristy J. Gotink, Henk J. Broxterman, Henk M.W. Verheul. Short-time exposure to high concentrations of sunitinib causes tumor cell death. [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 1621. doi:10.1158/1538-7445.AM2013-1621 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|