Natural Phenolic Acid,Product of the Honey Bee,for the Control of Oxidative Stress,Peritoneal Angiogenesis,and Tumor Growth in Mice |
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Authors: | Nada Oroli Martina Kunti Marina Kukolj Dyana Odeh Daniela An
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Institution: | 1.Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10000 Zagreb, Croatia; (M.K.); (M.K.); (D.O.);2.Agency for Medicinal Products and Medical Devices, Ksaverska cesta 4, HR-10000 Zagreb, Croatia; |
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Abstract: | Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 106) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity. |
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Keywords: | gallic acid caffeic acid Ehrlich ascites tumor angiogenesis macrophage activity proangiogenic factors mice |
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