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Berberine in breast cancer, a multi-targeted therapeutic agent from mechanisms to clinical translation.

Created on 30 Jun 2026

Authors

Haokun Yang, Xin Nian

Published in

Molecular biology reports. Volume 53. Issue 1. Jun 30, 2026. Epub Jun 30, 2026.

Abstract

Breast cancer remains a highly heterogeneous malignancy in which metastasis and therapeutic resistance represent the primary drivers of patient mortality. Berberine (BBR), a natural isoquinoline alkaloid, has emerged as a promising pleiotropic agent capable of simultaneously targeting multiple oncogenic vulnerabilities. In this Review, we systematically outline the multifaceted molecular mechanisms underlying the anti-tumor efficacy of BBR in breast cancer. We detail how BBR disrupts core intracellular signaling networks-specifically the PI3K/AKT/mTOR, MAPK/ERK, and Wnt/β-catenin pathways-and modulates the m6A RNA epitranscriptome via the METTL3/IGF2BP3 axis to induce apoptosis, enforce cell cycle arrest, and suppress the epithelial-mesenchymal transition (EMT). Beyond direct cytotoxicity, we highlight BBR's capacity to remodel the tumor microenvironment (TME) by suppressing cancer-associated fibroblasts (CAFs) and tumor angiogenesis, while simultaneously targeting treatment-resistant cancer stem cells (CSCs) through the epigenetic restoration of tumor-suppressive microRNAs. Furthermore, we discuss the role of BBR as a potent chemosensitizer capable of reversing multidrug resistance to augment conventional chemotherapeutic and endocrine regimens. Finally, we address the inherent pharmacokinetic bottlenecks that limit BBR's clinical translation and examine how cutting-edge nanomedicine platforms can circumvent these barriers, offering a comprehensive translational roadmap for integrating BBR into next-generation oncology therapeutics.

PMID:
42377770
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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