7-Deshydroxypyrogallin-4-carboxylic acid dietary phytochemical as a putative FTO inhibitor in breast cancer: an integrated computational and cytotoxicity study

Abstract

Abstract Breast cancer is the most frequently diagnosed malignancy in women globally, representing a major global health burden, with a significant subset of cases exhibiting resistance to standard therapeutic regimens. Recently, m 6 A RNA demethylases such as FTO have been identified as important oncogenes in breast cancer, which modify the epitranscriptome of tumor cells to favor expression of growth-promoting genes while suppressing expression of anti-apoptotic genes. In this study, we performed virtual screening of 1,000 dietary compounds targeting the FTO protein in order to discover potential therapies for breast cancer. 7-Deshydroxypyrogallin-4-carboxylic acid (DCA) was identified as the top-ranked candidate. Molecular dynamics (MD) simulations of DCA-FTO complex displayed the formation of stable hydrogen bonds for 200 ns of MD simulations. The ADMET-prediction of DCA showed high gastrointestinal tract absorption and is not expected to be Ames-toxic. The effect of DCA on the growth of MCF-7 human breast cancer cells was assessed by Sulforhodamine B (SRB) cytotoxicity assays and found to be dose- and time-dependent. The IC₅₀ values for the growth inhibition of MCF-7 breast cancer cells were found to be 90.7 µg/mL after 24 hours of treatment and 40.8 µg/mL after 48 hours. As a secondary exploratory analysis, lupinine was computationally evaluated against NQO1; however, its suboptimal binding stability and safety concerns preclude experimental advancement at this stage. These findings provide a preliminary mechanistic and experimental framework for DCA as a dietary FTO inhibitor in breast cancer, necessitating further validation through orthogonal target engagement assays, m 6 A quantification, and in vivo tumor models.