Abstract
BACKGROUND: Breast cancer (BC) ranks as the most prevalent cancer type among women globally. Nanoparticle technology, a promising approach, plays a crucial role in effective cancer diagnosis and treatment. In this context, researchers investigated the efficacy of BCc1 nanomedicine, which utilizes nanochelating technology and possesses anti-neoplastic properties, in mice with breast tumors. Notably, this study represents the first global exploration of BCc1 nanomedicine's potential to induce autophagy, a process mediated by autophagy-related genes (Beclin-1, ATG-4B, ATG-7, and mTOR), while evaluating tumor cell death. METHODS: In this study, female BALB/c mice bearing 4T1 mammary tumors received daily treatments with BCc1 nanomedicine for 24 consecutive days via two administration routes: intraperitoneal (i.p.) injection and oral administration by gavage. The research investigated the impact of BCc1 nanomedicine on autophagy induction. Importantly, BCc1 nanomedicine played a role in mitigating tumor cell death severity by activating essential genes. Real-time PCR facilitated detailed gene expression analysis during the 24-day treatment period. RESULTS: Cyclophosphamide and BCc1 nanomedicine exhibited distinct regulatory effects on autophagy-associated genes. Beclin-1 expression was significantly upregulated in both cyclophosphamide-treated and BCc1-administered groups compared to controls. In BCc1-treated mice, ATG-4B and ATG-7-genes essential for autophagosome formation and maturation-were markedly downregulated across all dosing regimens. Concurrently, BCc1 induced a significant reduction in mTOR expression, consistent with the removal of a major inhibitory checkpoint in autophagy initiation. Taken together, these findings suggest that BCc1 exerts a stage-specific influence on autophagy, potentially enhancing its initiation phase while attenuating subsequent maturation steps. CONCLUSION: In summary, BCc1 nanomedicine demonstrates therapeutic potential in BC, in part through the modulation of autophagy pathways. The observed gene expression profile-characterized by mTOR suppression and Beclin-1 upregulation alongside reduced ATG-4B and ATG-7 expression-indicates a selective enhancement of autophagy initiation, coupled with alterations in autophagosome maturation. This nuanced modulation of autophagy may contribute to BCc1's anti-tumor activity and warrants further investigation into its stage-specific mechanistic effects in cancer therapy.