Cisplatin plus TRAIL inhibits Wnt-1 signaling and increases apoptosis in cancer stem cells. Cancer stem cells derived from CRL2335 and MDA-MB-468 TNBC cells were treated with cisplatin, TRAIL or cisplatin plus TRAIL for 24 h. (A). Cancer stem cell extracts were prepared and analyzed for Wnt-1, phospho-β-catenin, β-catenin, cyclin D1, by Western blotting. Equal protein loading was compared with that of actin. (B). Cancer stem cell extracts were prepared and analyzed for DR4 and DR5 receptors by Western blotting. Equal protein loading was compared with that of actin. (C). Apoptosis was quantified by Cell Death ELISA and normalized to values measured in untreated cells. Cancer stem cells showed a significant increase in apoptosis in the presence of cisplatin plus TRAIL in comparison to untreated cells in CRL2335 (C) and MDA-MB-468 (D) derived CSCs (*p<0.001). Data are the mean ± SE of triplicate determinations.