Metastasis is responsible for the majority of cancer-related deaths and prevention
of metastasis remains a big challenge for cancer therapy. Cucurbitacin B (Cuc B) is
a natural triterpenoid with potent anticancer activities while its effect on metastasis
remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc
B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were
treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The
effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion
assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined.
The protein expression was determined by Western blotting. Cuc B (< 100 nmol·L −1
) showed no obvious cytotoxicity to MDA-MB-231 cells, but significantly inhibited
migration, invasion, and adhesion to Matrigel, fibronectin, type I collagen, and endothelial
cells. Cuc B dramatically inhibited the phosphorylation of focal adhesion kinase (FAK)
and paxillin in dose- and time-dependent manners. Furthermore, Cuc B induced intracellular
reactive oxygen species (ROS) generation, which could be reduced by N -acetyl-l-cysteine
(NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration
and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary,
Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231
cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.