| Autor: |
Santana MR; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil., Santos YBD; Molecular Modeling Laboratory, Department of Health, State University of Feira de Santana, Feira de Santana 44036-900, Brazil., Santos KS; Molecular Modeling Laboratory, Department of Health, State University of Feira de Santana, Feira de Santana 44036-900, Brazil., Santos Junior MC; Molecular Modeling Laboratory, Department of Health, State University of Feira de Santana, Feira de Santana 44036-900, Brazil., Victor MM; Department of Organic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador 40231-300, Brazil., Ramos GDS; Department of Organic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador 40231-300, Brazil., Nascimento RPD; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil., Costa SL; Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil.; National Institute of Translational Neuroscience (INNT), Rio de Janeiro 21941-902, Brazil. |
| Abstrakt: |
The molecular mechanisms underlying the observed anticancer effects of flavonoids remain unclear. Increasing evidence shows that the aryl hydrocarbon receptor (AHR) plays a crucial role in neoplastic disease progression, establishing it as a potential drug target. This study evaluated the potential of hydroxy flavonoids, known for their anticancer properties, to interact with AHR, both in silico and in vitro, aiming to understand the mechanisms of action and identify selective AHR modulators. A PAS-B domain homology model was constructed to evaluate in silico interactions of chrysin, naringenin, quercetin apigenin and agathisflavone. The EROD activity assay measured the effects of flavonoids on AHR's activity in human breast cancer cells (MCF7). Simulations showed that chrysin, apigenin, naringenin, and quercetin have the highest AHR binding affinity scores (-13.14 to -15.31), while agathisflavone showed low scores (-0.57 and -5.14). All tested flavonoids had the potential to inhibit AHR activity in a dose-dependent manner in the presence of an agonist (TCDD) in vitro. This study elucidates the distinct modulatory effects of flavonoids on AHR, emphasizing naringenin's newly described antagonistic potential. It underscores the importance of understanding flavonoid's molecular mechanisms, which is crucial for developing novel cancer therapies based on these molecules. |
