| Literature DB >> 30551509 |
Pavić Aleksandar1, Mitić-Ćulafić Dragana2, Jasnić Nebojša3, Nikolić Biljana3, Simin Nataša4, Vasiljević Branka5, Knežević-Vukčević Jelena3.
Abstract
The objective of this study was to evaluate potential of two chemically characterized edible wild onion species, Allium flavum and Allium carinatum, to reduce side effects of cytostatic doxorubicin (Dox). Since Dox application is mainly limited due to its high cardiotoxicity, while there are no approved cardioprotective agents for the prevention of Dox adverse effects, new co-treatments are urgently needed. Here, we showed that methanol extracts expressed high antioxidant activity and synergistically increased Dox anticancer activity against human hepatoma (HepG2) and lung carcinoma (A549) cells, while protected normal human fibroblasts (MRC-5) from Dox cytotoxicity. Analysis of the antioxidative enzymes level (catalase and superoxide dismutases) showed that the catalase level was differently altered in cancer cells compared to normal cells upon applied treatments. In vivo toxicity evaluation in the zebrafish model revealed significantly lower toxicity of extracts compared to Dox, and no teratogenic effects at applied doses. We found that extracts successfully rescued the Dox-treated embryos of life-threating cardiomyopathy, while at the same time reduced developmental toxicity and neutropenia. Further analysis demonstrated that extracts had higher anti-angiogenic activity than sunitinib or auranofin, clinically used antiangiogenic drugs. In addition, angiogenesis was markedly more suppressed in Dox-extract cotreatments than upon single treatments.Entities:
Keywords: Allium extracts; Anti-angiogenesis; Anticancer activity; Cardio- and myeloprotection; Doxorubicin; Zebrafish embryos
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Year: 2018 PMID: 30551509 DOI: 10.1016/j.biopha.2018.11.106
Source DB: PubMed Journal: Biomed Pharmacother ISSN: 0753-3322 Impact factor: 6.529