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

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 ≥1.50μM after 24h 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 168h). Furthermore, BrB treatment is associated with reduced DU145 clonogenicity in 2D cultures, as well as decreased area/volume of 3D tumor spheroids. Finally, BrB (6μM) reduced cell migration/invasion in 2D monolayers and promoted antimigratory effects in DU145 tumor spheroids (≥30μM). 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.