Cellular and Molecular Mechanisms of Berberine in Cancer Therapy: Recent Advances

In recent years, the role of traditional Chinese medicine (TCM) in comprehensive cancer treatment has become increasingly prominent, gradually emerging as an important adjunctive modality alongside conventional therapies such as surgery, chemotherapy, and radiotherapy, and attracting widespread attention. Berberine, an isoquinoline alkaloid extracted from natural plants such as Coptis chinensis, possesses broad-spectrum and potent pharmacological activities. A large body of evidence has demonstrated that berberine exerts definite antitumor effects in various cancer models, with its mechanisms of action spanning multiple dimensions, including cell-cycle arrest, induction of cell death, modulation of the tumor microenvironment (TME), inhibition of invasion and metastasis, and intervention in angiogenesis. Based on the latest research progress worldwide, this review focuses on key oncogenic signaling pathways and immune regulatory mechanisms to systematically elucidate the cellular and molecular mechanisms underlying the antitumor activity of berberine, and further discusses its clinical application potential and the challenges ahead. Although the clinical translation of berberine remains constrained by bottlenecks such as formulation optimization and bioavailability enhancement, its broad prospects in the field of cancer prevention and treatment establish it as a highly valuable TCM-derived antitumor candidate for further development.