Flavonoid brachydin B decreases viability, proliferation, and migration in human metastatic prostate (DU145) cells grown in 2D and 3D culture models

Juliana Mara Serpeloni; Diego Luis Ribeiro; Gabriela Fátima Weiss; Larissa Cristina Bastos de Oliveira; Andressa Yuri Fujiike; Higor Lopes Nunes; Claudia Quintino da Rocha; Roberta Losi Guembarovski; Ilce Mara de Syllos Cólus

doi:10.1093/toxres/tfad019

Flavonoid brachydin B decreases viability, proliferation, and migration in human metastatic prostate (DU145) cells grown in 2D and 3D culture models

Toxicol Res (Camb). 2023 Apr 1;12(2):321-331. doi: 10.1093/toxres/tfad019. eCollection 2023 Apr.

Authors

Juliana Mara Serpeloni¹, Diego Luis Ribeiro², Gabriela Fátima Weiss¹, Larissa Cristina Bastos de Oliveira¹, Andressa Yuri Fujiike¹, Higor Lopes Nunes¹, Claudia Quintino da Rocha³, Roberta Losi Guembarovski¹, Ilce Mara de Syllos Cólus¹

Affiliations

¹ Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Paraná, 86057-970, Brazil.
² Department of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, 14040-903, Brazil.
³ Department of Chemistry, Center for Exact Sciences and Technology, Federal University of Maranhão, São Luís, Maranhão, 65080-805, Brazil.

Abstract

Brachydin B (BrB) is a unique dimeric flavonoid extracted from Fridericia platyphylla (Cham.) LG Lohmann with different biological activities. However, the antitumoral potential of this flavonoid is unclear. In our study, we evaluated the effects of the BrB flavonoid on cell viability (MTT, resazurin, and lactate dehydrogenase assays), proliferation (protein dosage and clonogenic assay), and migration/invasion (3D ECM gel, wound-healing, and transwell assays) of metastatic prostate (DU145) cells cultured both as traditional 2D monolayers and 3D tumor spheroids in vitro. The results showed that the BrB flavonoid promotes cytotoxic effects from ≥1.50 μM after 24 h of treatment in DU145 cells in monolayers. In 3D prostate tumor spheroids, BrB also induced cytotoxic effects at higher concentrations after longer treatment (48, 72, and 168 h). Furthermore, BrB treatment is associated with reduced DU145 clonogenicity in 2D cultures, as well as decreased area/volume of 3D tumor spheroids. Finally, BrB (6 μM) reduced cell migration/invasion in 2D monolayers and promoted antimigratory effects in DU145 tumor spheroids (≥30 μM). In conclusion, the antitumoral and antimigratory effects observed in DU145 cells cultured in 2D and 3D models are promising results for future studies with BrB using in vivo models and confirm this molecule as a candidate for metastatic prostate cancer therapy.

Keywords: Arrabidaea brachyphoda; chemoprevention; cytotoxicity; metastasis; phytochemical; prostate cancer.