Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Matrine targets β-catenin and blocks the formation of β-catenin/TCF7L2 complex to promote ferroptosis and inhibit metastasis in triple-negative breast cancer.
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Sang Yazhou, Hu Yue, Liang Ruohan, Zhang Yueyue, Du Hongyuan, Zhang Huilan, Chen Juan, Zhang Yaqiong, Cao Xuan
Аннотация
BACKGROUND: Triple-negative breast cancer (TNBC) is still incurable, exhibiting a high propensity for metastasis. Matrine has been confirmed to possess anti-tumor properties. Nevertheless, the precise mechanism by which matrine inhibits TNBC metastasis remains uncertain.
PURPOSE: This investigation aimed to explore whether matrine could disrupt TNBC metastasis.
METHODS: The migratory capacity of TNBC cells was assessed via wound healing and transwell assays. Then, we evaluated whether matrine directly interacts with β-catenin (β-cat). Molecular docking combined with plasmid point mutation was employed to ascertain the specific amino acid binding sites of matrine and β-cat. Next, we evaluated the impact of matrine on the formation of β-cat/transcription factor 7 like 2 (TCF7L2) complex and whether matrine could induce ferroptosis (FPT) in TNBC. The mouse lung metastasis model was utilized to assess the potential of matrine in inhibiting TNBC metastasis.
RESULTS: Our research proved that matrine could directly target β-cat and abrogate the interaction of β-cat and TCF7L2, thus inhibiting the Wnt/β-cat downstream signaling pathway. Furthermore, matrine weakened the regulatory effect of TCF7L2 on glutathione peroxidase 4 (GPX4) and enhanced FPT by hindering the formation of the β-cat/TCF7L2 transcription complex. In addition, matrine-induced FPT effectively suppressed epithelial-mesenchymal transition (EMT) in TNBC.
CONCLUSIONS: This study demonstrates that matrine impedes the stimulation of the Wnt/β-cat pathway, has anti-metastatic effects on TNBC by triggering ferroptosis and inhibiting EMT.
PURPOSE: This investigation aimed to explore whether matrine could disrupt TNBC metastasis.
METHODS: The migratory capacity of TNBC cells was assessed via wound healing and transwell assays. Then, we evaluated whether matrine directly interacts with β-catenin (β-cat). Molecular docking combined with plasmid point mutation was employed to ascertain the specific amino acid binding sites of matrine and β-cat. Next, we evaluated the impact of matrine on the formation of β-cat/transcription factor 7 like 2 (TCF7L2) complex and whether matrine could induce ferroptosis (FPT) in TNBC. The mouse lung metastasis model was utilized to assess the potential of matrine in inhibiting TNBC metastasis.
RESULTS: Our research proved that matrine could directly target β-cat and abrogate the interaction of β-cat and TCF7L2, thus inhibiting the Wnt/β-cat downstream signaling pathway. Furthermore, matrine weakened the regulatory effect of TCF7L2 on glutathione peroxidase 4 (GPX4) and enhanced FPT by hindering the formation of the β-cat/TCF7L2 transcription complex. In addition, matrine-induced FPT effectively suppressed epithelial-mesenchymal transition (EMT) in TNBC.
CONCLUSIONS: This study demonstrates that matrine impedes the stimulation of the Wnt/β-cat pathway, has anti-metastatic effects on TNBC by triggering ferroptosis and inhibiting EMT.