Anti-metastatic effect of jolkinolide B and the mechanism of activity in breast cancer MDA-MB-231 cells

Tumor metastasis is the main cause of mortality in cancer patients. However, no effective therapies are currently available to prevent metastasis. Cell adhesion to the extracellular matrix (ECM) is crucial in cancer progression and metastasis. Thus, suppression of cell adhesion may be an effective therapeutic strategy for the prevention of metastasis. In the present study, the anti-adhesion and anti-invasion effects of jolkinolide B, a diterpenoid compound from Euphorbia fischeriana Steud, that were exerted through suppression of beta(1)-integrin expression and phosphorylation of focal adhesion kinase (FAK) were examined in human breast cancer MDA-MB-231 cells. Jolkinolide B inhibited the adhesion of MDA-MB-231 cells to fibronectin but not to poly-L-lysine. In addition, jolkinolide B inhibited extracellular signal-regulated kinase (ERK) phosphorylation. U0126, an ERK inhibitor, also suppressed the invasion and adhesion of MDA-MB-231 cells. Overall, the present data demonstrated that jolkinolide B is a novel inhibitor of FAK-mediated signaling pathways that is involved in decreasing cell adhesion and invasion. Mitogen-activated protein kinase/ERK kinase may play a critical role in these effects, indicating that jolkinolide B possesses therapeutic potential for the treatment of breast cancer metastasis.