PRJNA765810
Therapeutic effects of dietary soybean genistein on triple-negative breast cancer via regulation of epigenetic mechanisms
Consumption of dietary natural components such as genistein (GE) found in soy-rich sources is strongly associated with a lower risk of breast cancer. However, bioactive dietary component-based therapeutic strategies are largely understudied in breast cancer treatment. Our investigation sought to elucidate the potential mechanisms linking the bioactive dietary GE to its breast cancer chemotherapeutic potential in a special subtype of aggressive breast cancer, triple-negative breast cancer (TNBC), by utilizing two preclinical patient-derived xenograft (PDX) orthotopic mouse models. Our study revealed that administration of GE resulted in inhibition of tumor weight and tumor volume in both PDX models. With transcriptomics analyses in TNBC tumors isolated from PDXs, we found that dietary soybean GE significantly influenced multiple tumor-regulated gene expressions. Further validation assessment of six candidate differentially expressed genes (DEGs), Cd74, Lpl, Ifi44, Fzd9, Sat1 and Wwc1, demonstrated a similar trend at gene transcriptional and protein levels as observed in RNA-sequencing results. Additionally, our findings revealed that GE can modify expression levels of key epigenetic-associated genes such as DNA methyltransferases (Dnmt3b), ten-eleven translocation (Tet3) methylcytosine dioxygenases and histone deacetyltransferase (Hdac2), and their enzymatic activities as well as genomic DNA methylation and histone methylation (H3K9) levels. Collectively, our investigation shows high significance for potential development of a novel therapeutic approach by using bioactive soybean GE for TNBC patients who have few treatment options.