# FDI-6 inhibits VEGF-B expression in metastatic breast cancer: a combined in vitro and in silico study

## TL;DR

This study shows that FDI-6 reduces VEGF-B expression in metastatic breast cancer cells and may inhibit angiogenesis through interactions with VEGFR1.

## Contribution

The novel finding is FDI-6's interaction with VEGFR1 and its cell-type-specific effects on VEGF-B expression in breast cancer.

## Key findings

- FDI-6 significantly reduces cell viability in MDA-MB-231 cells with an IC50 of 10.8 μM.
- FDI-6 suppresses wound closure in MDA-MB-231 cells but not in HUVEC cells.
- Molecular docking and simulations show stable interaction of FDI-6 with VEGFR1.

## Abstract

Angiogenesis is the process by which new blood vessels are formed to meet the oxygen and nutrient needs of tissues. This process is vitally important in many physiological and pathological conditions such as tumor growth, metastasis, and chronic inflammation. Although the relationship of FDI-6 compound with FOXM1 protein is well known in the literature, its relationship with angiogenesis is not adequately elucidated. This study investigates the relationship of FDI-6 with angiogenesis and vascular endothelial growth factor B (VEGF-B) protein expression alterations. Furthermore, the study aims to elucidate the in silico interaction of FDI-6 with the VEGFR1 protein, a key player in initiating the angiogenic process, which is activated through its binding with VEGF-B. Our results demonstrate a significant effect of FDI-6 on cell viability. Specifically, we determined that the IC50 value of FDI-6 in HUVEC cells after 24 h of treatment is 24.2 μM, and in MDA-MB-231 cells after 24 h of application, it is 10.8 μM. These findings suggest that the cytotoxic effect of FDI-6 varies depending on the cell type. In wound healing experiments, FDI-6 significantly suppressed wound closure in MDA-MB-231 cells but did not show a similar effect in HUVEC cells. This finding suggests FDI-6 may have potential cell-type-specific effects. Molecular docking studies reveal that FDI-6 exhibits a stronger interaction with the VEGFR1 protein compared to its inhibitor, a novel interaction not previously reported in the literature. Molecular dynamic simulation results demonstrate a stable interaction between FDI-6 and VEGFR1. This interaction suggests that FDI-6 might modulate mechanisms associated with angiogenesis. Our Western blot analysis results show regulatory effects of FDI-6 on the expression of the VEGF-B protein. We encourage exploration of FDI-6 as a potential therapeutic agent in pathological processes related to angiogenesis. In conclusion, this study provides a detailed examination of the relationship between FDI-6 and both the molecular interactions and protein expressions of VEGF-B. Our findings support FDI-6 as a potential therapeutic agent in pathological processes associated with angiogenesis.