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Nutrients 2019, 11(4), 858; https://doi.org/10.3390/nu11040858

A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound

1
Department of Pharmacognosy, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
2
Pharmazentrum Frankfurt/ZAFES, Institute of General Pharmacology and Toxicology, Clinic of the Goethe University, D-60590 Frankfurt/Main, Germany
3
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
4
Department of Toxicology, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
5
Department of Drug Analysis, Chemistry of the Environment and Food, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
6
OncoGen Centre, “Pius Brînzeu” Emergency County Hospital, 156, Liviu Rebreanu Boulevard, 300736 Timişoara, Romania
7
Department of Functional Sciences, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
8
Department of Pharmaceutical Physics, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
9
Department of Pharmaceutical Chemistry, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
10
Department of Functional Sciences—Pathophysiology, “Victor Babeş” University of Medicine and Pharmacy, 2, Eftimie Murgu Square, 300041 Timişoara, Romania
*
Author to whom correspondence should be addressed.
Received: 12 February 2019 / Revised: 4 April 2019 / Accepted: 12 April 2019 / Published: 16 April 2019
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Abstract

Apigenin (4′,5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 μM and 60 μM. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabolic activity of human dendritic cells (DCs) under LPS-activation was clearly attenuated by stimulation with high concentrations of Api. Il-6 and IL-10 secretion was almost completely blocked while TNF alpha secretion was reduced by about 60%. Api elicited antiangiogenic properties in a dose-dependent manner. Both concentrations of Api influenced tumour cell growth and migration, inducing a limited tumour area inside the application ring, associated with a low number of capillaries. View Full-Text
Keywords: apigenin; A375 human melanoma cell line; proliferation; apoptosis; mitochondrial bioenergetics and glycolysis; angiogenesis apigenin; A375 human melanoma cell line; proliferation; apoptosis; mitochondrial bioenergetics and glycolysis; angiogenesis
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Ghițu, A.; Schwiebs, A.; Radeke, H.H.; Avram, S.; Zupko, I.; Bor, A.; Pavel, I.Z.; Dehelean, C.A.; Oprean, C.; Bojin, F.; Farcas, C.; Soica, C.; Duicu, O.; Danciu, C. A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound. Nutrients 2019, 11, 858.

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