Isorhamnetin inhibits migration and promotes apoptosis via modulation of oxidative stress, mitochondrial dysfunction, and the TIGIT/CD155 axis in 4T1 breast cancer cells

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Background: Isorhamnetin (ISO), a natural flavonoid derived from traditional Chinese medicine, has demonstrated potential antitumor activity. This study aimed to investigate the effects of ISO on the proliferation, migration, and apoptosis of mouse breast cancer 4T1 cells and to explore the underlying mechanisms. Methods: Cell viability was evaluated using a Cell Counting Kit-8 (CCK-8) assay. Wound healing and colony formation assays were performed to assess migration and clonogenic ability. Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were measured to evaluate oxidative stress and mitochondrial function. Quantitative polymerase chain reaction and Western blot analyses were conducted to determine the expression of the TIGIT/CD155 signaling axis. Results: ISO inhibited 4T1 cell proliferation in a concentration- and time-dependent manner. It significantly reduced migration and clonogenic capacity. ISO treatment increased intracellular ROS levels and disrupted mitochondrial membrane potential, indicating oxidative stress-mediated mitochondrial dysfunction. Additionally, ISO markedly downregulated the mRNA and protein expression levels of the TIGIT/CD155 signaling axis (p < 0.01). Conclusion: ISO suppresses proliferation and migration and induces apoptosis in 4T1 breast cancer cells, potentially through modulation of oxidative stress, mitochondrial dysfunction, and the TIGIT/CD155 signaling axis. These findings provide mechanistic insight into the antitumor effects of ISO and support its potential as a therapeutic candidate for breast cancer.