D430-2307 inhibits breast cancer cell growth by dual induction of apoptosis and G0/G1 arrest via phosphatidylinositol 3-kinase/protein kinase B signaling.

Abstract

D430-2307 is a novel small-molecule compound identified through virtual screening of the Chemdiv database that markedly inhibited the proliferation of both MCF-7 and MDA-MB-231 breast cancer cells. In the present study, the anticancer activity and underlying molecular mechanisms of D430-2307 were investigated. Thiazolyl blue, colony formation, wound healing, and transwell assays were performed to assess the effects of D430-2307 on breast cancer cell proliferation, migration, and invasion. To elucidate the underlying mechanisms, flow cytometry, Western blotting, and fluorescence staining were performed to analyze cell-cycle distribution, apoptosis, and intracellular reactive oxygen species (ROS) levels. In addition, network pharmacology, transcriptomics, and bioinformatics analyses were integrated to identify core targets and associated pathways, while molecular docking was performed to verify target-ligand interactions. The results demonstrated that D430-2307 significantly inhibited breast cancer cell proliferation, migration and invasion, induced G 0 /G 1 cell cycle arrest, downregulated CDK4/6 expression, and promoted apoptosis through modulation of the Bax/Bcl-2 ratio and activation of caspase-3/7 signaling. Furthermore, D430-2307 suppressed the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway via elevation of intracellular ROS levels. These findings suggest that D430-2307 exerts antitumor effects through ROS-mediated suppression of PI3K/AKT signaling, G 0 /G 1 cell cycle arrest, and apoptosis induction, providing a foundation for the development of novel anti-breast cancer therapeutics.