A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound.
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.
['Ghițu|Alexandra|A|', 'Schwiebs|Anja|A|', 'Radeke|Heinfried H|HH|', 'Avram|Stefana|S|', 'Zupko|Istvan|I|0000-0003-3243-5300', 'Bor|Andrea|A|', 'Pavel|Ioana Zinuca|IZ|', 'Dehelean|Cristina Adriana|CA|', 'Oprean|Camelia|C|', 'Bojin|Florina|F|', 'Farcas|Claudia|C|', 'Soica|Codruta|C|', 'Duicu|Oana|O|', 'Danciu|Corina|C|']
D000255:Adenosine Triphosphate D020533:Angiogenesis Inhibitors D000893:Anti-Inflammatory Agents D000972:Antineoplastic Agents, Phytogenic D047310:Apigenin D017209:Apoptosis D053148:Caspase 3 D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D016207:Cytokines D003713:Dendritic Cells D004032:Diet D006801:Humans D007155:Immunologic Factors D007249:Inflammation D007770:L-Lactate Dehydrogenase D008070:Lipopolysaccharides D019684:Magnoliopsida D008545:Melanoma D008928:Mitochondria D008517:Phytotherapy D010936:Plant Extracts
apigenin A375 human melanoma cell line apoptosis angiogenesis mitochondrial bioenergetics and glycolysis proliferation