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.
Highlights
Natural products, either in the form of total extracts or purified active compounds, have been demonstrated to play a vital role in the current management of different types of cancer, with directions being pulled toward both treatment and prevention
Within this study we assessed the Api effect on cellular bioenergetics in A375 human measured at 72 h post-treatment of A375 human melanoma cells with two concentrations of Api
Our results indicate a significant alteration of the bioenergetic profile in A375 human melanoma cells treated with 60 μM Api, an effect that might emphasise its beneficial properties against tumour cells
Summary
Either in the form of total extracts or purified active compounds, have been demonstrated to play a vital role in the current management of different types of cancer, with directions being pulled toward both treatment and prevention. As proven by current cancer therapy, an increased number of anticancer drugs used in the clinic are based on natural products obtained from different sources (plants, animals, microorganisms) [1]. 1% of the types of skin cancers, it is the most dangerous form, as it is responsible for most death cases. The number of papers on PubMed that have the word “melanoma” in their title exceeds 120,000, indicating that melanoma represents a continuing hot topic that is being approached by an impressive number of different therapeutic strategies
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