# Nanochelate-based BCc1 delivery and its impact on key regulatory pathways in BALB/c breast cancer: An analysis of Beclin-1, ATG-4B, ATG-7, and mTOR expression

## TL;DR

This study explores how a new nanomedicine called BCc1 affects breast cancer in mice by influencing autophagy, a cellular process linked to tumor cell death.

## Contribution

This is the first study to investigate BCc1's effect on autophagy-related genes in breast cancer, revealing its potential as a novel therapeutic.

## Key findings

- BCc1 nanomedicine upregulates Beclin-1 and downregulates ATG-4B and ATG-7, suggesting autophagy initiation.
- BCc1 significantly reduces mTOR expression, removing an inhibitory checkpoint in autophagy.
- BCc1 shows anti-neoplastic properties in BALB/c mice with breast tumors.

## Abstract

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.

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.

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.

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.

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•BCc1 nanomedicine demonstrates therapeutic potential in breast cancer.•The efficacy of BCc1 nanomedicine possesses anti-neoplasmic properties, in mice with breast tumors.•BCc1 nanomedicine's capacity to induce autophagy.•Enhancement of autophagy initiation characterized by mTOR suppression and Beclin-1 upregulation alongside reduced ATG-4B and ATG-7 expression.

BCc1 nanomedicine demonstrates therapeutic potential in breast cancer.

The efficacy of BCc1 nanomedicine possesses anti-neoplasmic properties, in mice with breast tumors.

BCc1 nanomedicine's capacity to induce autophagy.

Enhancement of autophagy initiation characterized by mTOR suppression and Beclin-1 upregulation alongside reduced ATG-4B and ATG-7 expression.