# Fumiquinazolines F and G from the Fungus Penicillium thymicola Demonstrates Anticancer Efficacy Against Triple-Negative Breast Cancer MDA-MB-231 Cells by Inhibiting Epithelial–Mesenchymal Transition

## TL;DR

Fumiquinazolines F and G from a fungus show anticancer effects by reducing breast cancer cell growth and migration through inhibiting epithelial–mesenchymal transition.

## Contribution

The study reveals fumiquinazolines F and G as novel compounds that inhibit triple-negative breast cancer by targeting epithelial–mesenchymal transition.

## Key findings

- Fumiquinazoline F effectively inhibits proliferation of both hormone-dependent and triple-negative breast cancer cells.
- The compound reduces cell migration and alters EMT-related protein levels in MDA-MB-231 cells.
- Fumiquinazolines show low cytotoxicity but significantly slow cell cycle progression in breast cancer cells.

## Abstract

The secondary metabolites of the fungus Penicillium thymicola, fumiquinazolines F and G, have antibacterial and antifungal characteristics; however, their potential anti-tumor action against human cancer cells remains unknown. The goal of our study was to determine the biological efficacy of fumiquinazolines F and G on breast and prostate cancer cells. Cancer cell proliferation and migration were monitored in real time using xCELLigence technology and flow cytometry. Alterations in mRNA and protein expression were assessed by RT-qPCR, ELISA, and Western blotting. Our data indicate that fumiquinazolines F and G are more effective in inhibiting breast cancer cell proliferation than prostate cancer cells. Fumiquinazoline F is active against both hormone-dependent epithelial MCF-7 (IC50 48 μM) and hormone-resistant triple-negative mesenchymal MDA-MB-231 breast cancer cells (IC50 54.1 μM). The metabolite has low cytotoxicity but slows cell cycle progression. In fumiquinazoline F-treated MDA-MB-231 cells, the levels of proteins implicated in epithelial–mesenchymal transition (EMT) (such as E-cadherin, vimentin, and CD44) fluctuate, resulting in a decrease in cell migratory rate and adhesion to a hyaluronic acid-coated substrate. Thus, fumiquinazolines F and G exhibit anticancer activity by inhibiting EMT, cell proliferation, and migration, hence reverting malignant cells to a less pathogenic phenotype. The compound’s multi-target anticancer profile underscores its potential for further exploration of novel EMT-regulating pathways.