Combinative treatment of Curdione and docetaxel triggers reactive oxygen species (ROS)-mediated intrinsic apoptosis of triple-negative breast cancer cells

Traditional Chinese medicine Curcuma zedoary has been used for treating various diseases and cancers. However, the therapeutic effect of Curdione, one of its major components in triple negative breast cancer (TNBC) is still obscure. This study is aimed to explore whether combination of Curdione and docetaxel (DTX) could strengthen the DTX-induced pro-apoptotic effects in TNBC cells and identify its involved signaling pathways. In this study, combination of Curdione and DTX intensified the inhibited MDA-MB-468 cell proliferation and increased cell apoptosis caused by DTX treatment alone. Moreover, the combinative treatment of Curdione and DTX synergistically potentiated DTX-induced cell apoptosis by triggering reactive oxygen species (ROS) generation. Co-treatment with NAC (ROS inhibitor) could mostly block the effects induced by combination of Curdione and DTX. SB203580 (p38 inhibitor) or SC-79 (Akt activator) could partly reverse the effects induced by co-treatment, indicating that mitogen-actived protein kinases (MAPKs) and the phosphatidylinositol 3-kinases (PI3K) /Akt signaling pathway were involved in the co-treatment induced ROS-mediated cell apoptosis. To sum up, combination of Curdione and DTX enhanced the chemotherapeutic efficacy on MDA-MB-468 cells by triggering ROS-mediated cell apoptosis via MAPKs and PI3K/Akt signaling pathways. Curdione combined with DTX might have potentials application as the therapeutic strategy for TNBC. ABBREVIATIONS: TNBC: triple negative breast cancer; ROS: reactive oxygen species; NAC: N-acetyl-L-cysteine; DTX: docetaxel; MAPKs: mitogen-actived protein kinases; PI3K/Akt: phosphatidylinositol 3-kinases (PI3K) /Akt; NF-Κb: the nuclear factor κB (NF-κB)