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2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702

Abstract

Background

Androgen receptor mutations, particularly T877A and W741L, promote prostate cancer (PCa). The main therapies against PCa use androgen receptor (AR) antagonists, including Bicalutamide; but these drugs lose their effectiveness over time. Chrysin is a flavonoid with several biological activities, including antitumoral properties; however, its potential as an antiandrogen must be explored.

Objective

The present study aimed to characterize and compare the molecular interactions of chrysin with wild-type and mutated ARs and their cytotoxic effect in an model of PCa.

Methods

The affinities and molecular interactions of Bicalutamide and chrysin for the wild-type and mutated forms of AR were assessed by molecular docking. The MTT assay was used to evaluate the cytotoxic effect of these ligands on the DU-145 (T877A) and PC3 (W741L) PCa cell lines and on non-tumoral RWPE-1 cells.

Results

The molecular dockings predicted a higher affinity of chrysin for the mutated ARs than the wild-type AR (WT-AR); meanwhile, Bicalutamide presented a higher affinity for WT-AR. The amino acid residues involved in molecular interactions within the binding site of these receptors changed according to the ligands and AR variants, affecting their affinity scores. Chrysin exerted a specific cytotoxic effect against the PCa tumoral cells but none against the non-tumoral cells. In contrast, Bicalutamide showed potent cytotoxicity against all cell lines. Thus, the cytotoxic effect of chrysin against the DU-145 and PC3 cell line may be related to its strong and specific molecular interaction with the mutated ARs.

Conclusion

This study evidences the potential antiandrogen effect of chrysin on mutated ARs and specific cytotoxicity against PCa cells, suggesting that this flavonoid for therapy of advanced PCa.

© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-07-18
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  • Article Type:
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Keyword(s): Androgen receptor; Bicalutamide; Chrysin; Molecular docking; Prostate cancer; T877A; W741L
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