A curcumin analog CA-5f inhibits urokinase-type plasminogen activator and invasive phenotype of triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is one of the most aggressive types of breast cancer with poor outcomes. Patients with TNBC cannot benefit from targeted therapies such as Tamoxifen and Herceptin. The aim of the present study was to seek a preventive or therapeutic agent with a potential inhibitory effect on aggressive progression of TNBC. Anticancer effect of a natural compound curcumin have been demonstrated, however, development of more effective curcumin analogs with better bioavailability is needed. We investigated if a curcumin analog CA-5f could inhibit the invasive phenotype of TNBC cell lines in the present study. Treatment with CA-5f inhibited the viability of MDA‑MB‑231 and Hs578T TNBC cells, possible by inducing apoptosis. The invasive phenotypes of these cells were inhibited by CA-5f in a concentration-dependent manner. Protein expression of urokinase-type plasminogen activator (uPA), a serine protease known to degrade the extracellular matrix and lead to invasion, was markedly decreased by CA-5f in Hs578T cells. However, mRNA level of uPA was not altered by CA-5f, implicating that the effect of CA-5f was not through transcriptional regulation. Of note, CA-5f upregulated plasminogen activator inhibitor type (PAI)-1, which is known to inhibit uPA by interacting with urokinase-type plasminogen receptor, in TNBC cells. Taken together, these results demonstrated that CA-5f significantly inhibited the invasive phenotype of TNBC cells, possibly by decreasing the protein level of uPA through upregulating PAI-1. Our results may provide useful information on developing CA-5f as a potential therapeutic agent against malignant progression of TNBC.