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

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 ?M and 60 ?M. 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.

SUBMITTER: Ghitu A

PROVIDER: S-EPMC6521017 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Ghițu Alexandra A Schwiebs Anja A Radeke Heinfried H HH Avram Stefana S Zupko Istvan I 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

Nutrients 20190416 4

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 m ...[more]

PMID: 30995771

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Project description:Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (CelebrexM-BM-.) is a selective cyclooxygenase-2 (COX-2) inhibitor wich exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of combination, we investigated the expression profile of the combination-treated liver cancer cell lines, using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes, functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell line displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semiquantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomics analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies. To identify new potential mechanisms of combined action of celecoxib and sorafenib, their effects on global gene expression in both cell lines were investigated and compared using the DNA microarray technology. Agilent 44K Human Whole Genome Oligonucleotide Microarrays (containing ~44,000 genes) were used to identify global gene expression changes in the HepG2 and Huh7 hepatocellular carcinoma (HCC) cell lines, following simultaneous treatment with 50 M-BM-5M celecoxib and 7.5 M-BM-5M sorafenib for 48 hours. All microarray experiments (a total of four) were performed in duplicates applying dye-swaps to avoid labeling bias.

Dataset Information

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

Publications

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

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