Pantnagar Journal of Research

Abstract

Cancer remains a leading cause of mortality worldwide, with breast cancer being one of the most prevalent and aggressive malignancies in women. A subpopulation of breast cancer cells, known as breast cancer stem cells (BCSCs), drives tumor initiation, progression, metastasis, and therapeutic resistance due to their self-renewal and pluripotency. The Wnt/β-catenin signaling pathway is crucial for maintaining BCSC properties, with β-catenin serving as a central effector that promotes stemness, survival, and tumor relapse. Conventional therapies often fail to eliminate BCSCs, resulting in poor prognosis and frequent recurrence. Natural compounds like curcumin exhibit anticancer activity with minimal side effects, yet their clinical utility is limited by low bioavailability and efficacy. To overcome these challenges, we designed a curcumin-glucose bioconjugate aimed at inhibiting β-catenin (PDB ID: 7AFW) in BCSCs. Molecular docking studies of curcumin, glucose, selected bioconjugate, and a known β-catenin binder (R9Q) revealed that the curcumin-glucose conjugate effectively interacts with key residues of β catenin, suggesting potential inhibition of signaling. By targeting β-catenin, the conjugate is expected to disrupt BCSC self renewal and survival, thereby impacting the breast cancer cell population and reducing tumor progression and relapse. These in silico findings provide a foundation for further in vitro and in vivo studies to validate the curcumin-glucose bioconjugate as a promising therapeutic strategy against breast cancer stem cells.