Interactions between genistein and Wnt pathway in colon adenocarcinoma and early embryos

The Wnt signaling pathway is one of the most ancient and pivotal signaling cascades, governing diverse processes in development and cancer regulation. Within the realm of cancer treatment, genistein emerges as a promising candidate due to its multifaceted modulation of various signaling pathways, including the Wnt pathway. Despite promising preclinical studies, the precise mechanisms underlying genistein's therapeutic effects via Wnt modulation remain elusive. In this study, we unveil novel insights into the therapeutic mechanisms of genistein by elucidating its inhibitory effects on Wnt signaling through macropinocytosis. Additionally, we demonstrate its capability to curtail cell growth, proliferation, and lysosomal activity in the SW480 colon adenocarcinoma cell model. Furthermore, our investigation extends to the embryonic context, where genistein influences gene regulatory networks governed by endogenous Wnt pathways. Our findings shed light on the intricate interplay between genistein, Wnt signaling, membrane trafficking, and gene regulation, paving the way for further exploration of genistein's therapeutic potential in cancer treatment strategies. Overall design: To investigate how genistein treatment affects gene regulatory networks during development, we treated Xenopus embryos with genistein at the 4-cell stage and collected them at stage 9.5 for RNA sequencing. In addition to genistein, we used two established Wnt activators: BIO (6-bromoindirubin-3'-oxime) and Chiron (CHIR 99021). All four conditions were profiled in triplicates and used for differential gene expression analysis.