Differential Toxicity of Anthracyclines on Cultured Endothelial Cells

التفاصيل البيبلوغرافية
العنوان: Differential Toxicity of Anthracyclines on Cultured Endothelial Cells
المؤلفون: Gur P. Kaushal, Varsha Kaushal, Paulette Mehta
المصدر: Endothelium. 11:253-258
بيانات النشر: Informa UK Limited, 2004.
سنة النشر: 2004
مصطلحات موضوعية: Time Factors, Anthracycline, Endothelium, Cell Survival, Physiology, Daunorubicin, DNA Fragmentation, Pharmacology, Western blot, polycyclic compounds, medicine, Humans, Idarubicin, Anthracyclines, Doxorubicin, medicine.diagnostic_test, Caspase 3, Chemistry, Endothelial Cells, Cell Biology, General Medicine, medicine.anatomical_structure, Caspases, Toxicity, Endothelium, Vascular, Tumor Suppressor Protein p53, medicine.drug, Artery
الوصف: Anthracyclines are known for their endothelial toxicity. Newer derivatives may have fewer toxic effects on endothelium. The authors therefore evaluated the effects of doxorubicin, doxorubicin analogs (daunorubicin, idarubicin), and pegylated liposomal doxorubicin (doxil) in human coronary artery endothelial cells (HCAECs). Endothelial viability did not change significantly with doxil, but was decreased with doxorubicin, daunorubicin, or idamycin. Similarly caspase-3 activity was significantly elevated in HCAECs treated with doxorubicin, daunorubicin, and idamycin. In contrast, doxil did not cause significant increase in caspase activity. The authors also characterized the levels of antiapoptotic and prosurvival proteins using Western blot analysis. There was no significant difference in the expression levels of Bcl-2, Bax, and phospho-Akt in endothelial cells treated with anthracycline derivatives. However, the expression levels of Mcl-l protein were unaltered in endothelial cells treated with doxil but were significantly decreased when treated with other anthracycline analogs. Doxil minimally affected the expression levels of p53, whereas other anthracyclines induced p53 protein levels to a significant level, resulting in endothelial cell apoptosis. The authors conclude that the liposomal anthracycline protects endothelial cells from injury by preventing caspase-3 activation and maintaining the expression of antiapoptotic molecule Mcl-1.
تدمد: 1029-2373
1062-3329
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39730a9d3e7a4de76d63e22b97073649Test
https://doi.org/10.1080/10623320490904124Test
رقم الانضمام: edsair.doi.dedup.....39730a9d3e7a4de76d63e22b97073649
قاعدة البيانات: OpenAIRE