1. Wild edible onions — Allium flavum and Allium carinatum — successfully prevent adverse effects of chemotherapeutic drug doxorubicin
- Author
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Jasnic Nebojsa, Mitić-Ćulafić Dragana, Simin Nataša, Nikolić Biljana, Knežević-Vukčević Jelena, Pavić Aleksandar, and Vasiljević Branka
- Subjects
0301 basic medicine ,Auranofin ,Drug-Related Side Effects and Adverse Reactions ,Allium flavum ,Developmental toxicity ,RM1-950 ,Pharmacology ,Zebrafish embryos ,Anticancer activity ,Allium ,Superoxide dismutase ,03 medical and health sciences ,0302 clinical medicine ,Anti-angiogenesis ,Onions ,medicine ,polycyclic compounds ,Animals ,Humans ,Doxorubicin ,Zebrafish ,Cardiotoxicity ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,biology ,Plant Extracts ,Chemistry ,Hep G2 Cells ,General Medicine ,biology.organism_classification ,3. Good health ,Cardio- and myeloprotection ,030104 developmental biology ,A549 Cells ,030220 oncology & carcinogenesis ,Allium extracts ,Cancer cell ,Toxicity ,biology.protein ,Therapeutics. Pharmacology ,medicine.drug - 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.
- Published
- 2019