A natural coumarin, benjaminin, suppresses proliferation and migration and induces apoptosis in MCF-7 breast cancer cells

Breast cancer remains the leading cause of cancer-related mortality in women, highlighting the need for selective and effective therapeutics. Conventional chemotherapies are often limited by off-target toxicity, prompting interest in natural products, including coumarins from Calophyllum species. Benjaminin, a novel coumarin, has demonstrated cytotoxicity in multiple cancer models, yet its effects in breast cancer remain unexplored. Here, we evaluated benjaminin in MCF-7 (tumorigenic) and MCF-10A (non-tumorigenic) breast cells. Benjaminin exhibited moderate but highly selective cytotoxicity toward MCF-7 cells while sparing normal epithelial cells. Mechanistic analyses revealed pronounced G1-phase arrest and apoptotic induction, confirmed by propidium iodide and Annexin V-FITC staining. Protein array profiling indicated upregulation of DR6 and Bax, consistent with activation of a non-classical extrinsic apoptotic pathway with mitochondrial priming. Functional assays demonstrated impaired migration and spreading, associated with lamellipodia loss and cytoskeletal disorganization, consistent with disruption of pathways involving cyclin D1-paxillin-Rac1-Arp2/3 signaling. These findings indicate that benjaminin may exert coordinated, multi-level anticancer effects, potentially connecting cyclin D1 downregulation with cell-cycle arrest, cytoskeletal dysregulation, apoptotic activation, and reduced migratory behavior. This study provides the first integrated mechanistic characterization of benjaminin in breast cancer cells and supports further investigation in additional subtypes, in vivo models, and pathway-specific analyses.