Green-synthesized rhein-selenium nanoparticles exhibit potent and highly selective anticancer activity against colon cancer via apoptosis and gene regulation

Abstract

Introduction: Colon cancer remains a major global health challenge, necessitating the development of novel, selective, and sustainable therapeutic strategies. Rhein, a bioactive anthraquinone isolated from Cassia italica, has demonstrated anticancer potential but suffers from limited bioavailability. To overcome these limitations, we investigated the green biosynthesis of Rhein-selenium nanoparticles (Rh-Se-NPs) and evaluated their anticancer efficacy. Methods: Rhein was extracted from Cassia italica leaves and confirmed by 1H and 13C nuclear magnetic resonance spectroscopy. Rh-Se-NPs were synthesized via a green biosynthetic approach and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Cytotoxicity was assessed against DLD-1 and SW620 colon cancer cell lines, with FSU fibroblast cells serving as controls. Cell proliferation, migration, and apoptosis were evaluated through morphological analysis, wound healing assays, caspase activity measurements, and gene expression profiling of oncogenes and tumor suppressors. Results and Discussion: Rh-Se-NPs exhibited spherical morphology (32 ± 5 nm, TEM), a hydrodynamic diameter of 90.4 nm (DLS), and high colloidal stability (zeta potential: 31.1 mV). Compared to free Rhein, Rh-Se-NPs demonstrated significantly enhanced cytotoxicity, reducing IC50 values by more than two-fold and increasing selectivity indices to 12.85 (DLD-1) and 6.93 (SW620). Functional assays confirmed inhibition of cell proliferation and migration. Apoptosis was evidenced by elevated caspase-9 and caspase-3 activities. Gene expression analysis revealed strong downregulation of oncogenes (CEA, FOXQ1, CXCL17, VEGFA) and marked upregulation of the tumor suppressor PTEN (up to 15.9-fold). This study demonstrates, for the first time, that Rh-Se-NPs act as a biocompatible phytochemical-selenium nanoplatform with dual anticancer mechanisms: apoptosis induction and oncogene suppression. The findings highlight Rh-Se-NPs as a promising, sustainable, and highly selective therapeutic strategy for colon cancer.