Üvez, AyçaEsener, Osman Behzat BurakErkısa, MerveKarakuş, DilekArmutak, Elif İlkay2023-10-092023-10-092020Üvez, A. vd. (2020). "Synergistic interactions between resveratrol and doxorubicin inhibit angiogenesis both in vitro and in vivo". Polish Journal of Veterinary Sciences, 23(4), 571-580.1505-17732300-2557https://doi.org/10.24425/pjvs.2020.135803https://journals.pan.pl/dlibra/publication/135803/edition/118729/contenthttp://hdl.handle.net/11452/34257Resveratrol is a polyphenolic compound which is found in many nutrients including grapes, peanuts, raspberries, and apples. Anti-proliferative, anti-angiogenic and apoptotic effects of resveratrol have been shown on various cancer cells. Doxorubicin is considered as one of the most effective anticancer agents and reveals its antitumor activity by induction of apoptosis and inhibition of angiogenesis. Our study reports for the first time the potent ability of resveratrol in combination with doxorubicin to inhibit angiogenesis in vitro and in vivo. The cytotoxic effect of resveratrol (1.56-100 mu M), doxorubicin (0.01-0.92 mu M) and their combination were analyzed in the human umbilical vein endothelial cells (HUVECs) by ATP assay. In vitro angiogenesis was evaluated using tube formation assay in HUVECs. In vivo anti-angiogenic activity was assessed in a chick chorioallantoic membrane (CAM) model using fertilized chicken eggs. All test groups were compared to thalidomide as a positive control, three concentrations of resveratrol (10-5-2.5 mu g/pellet) and a 2 mu g/pellet concentration of doxorubicin was examined. All data were evaluated statistically. Resveratrol and doxorubicin alone displayed inhibitory effects on angiogenesis and cell viability at higher doses. However, the combination of resveratrol and doxorubicin exhibited a significant dose-dependent inhibition of CAM angiogenesis in vivo as well as proliferation and tube formation in HUVECs compared to the positive control (+/-)-thalidomide. Our results suggest that resveratrol in combination with doxorubicin is a novel strategy in the prevention and treatment of angiogenesis.eninfo:eu-repo/semantics/openAccessVeterinary sciencesResveratrolAnti-angiogenic activityTube formationHuvecDoxorubicinChick chorioallantoic membraneCancerCombinationApoptosisGrowthChemotraphyCellsAnimalsAntibioticsAntineoplasticChorioallantoic membraneDrug synergismHuman umbilical vein endothelial cellsNeovascularizationPhysiologicResveratrolArticle0006049551000122-s2.0-8510032810757158023433480492Veterinary sciencesResveratrol; Resveratrol-4'-O-Glucuronide; Stilbene DerivativeAdenosine triphosphatDoxorubicinResveratrolThalidomideAntineoplastic antibioticAntioxidantDoxorubicinResveratrolAnimal cellAnimal experimentAntiangiogenic activityAntiproliferative activityArticleCell viabilityChick embryoChorioallantoisControlled studyDrug cytotoxicityDrug potentiationHumanHuman cellIn vitro studyIn vivo studyMouseNonhumanUmbilical vein endothelial cellAngiogenesisAnimalAngiogenesisCell proliferationCell survivalDrug effectDrug potentiationVascularization