Tremendous efforts have been made to improve the anticancer value of cisplatin [14–17]. Naturally occurring compounds from diets or medicinal plants are good candidates for increasing cisplatin’s anticancer

activity [18, 19]. The search for new compounds with high chemosensitization efficiency has never stopped. Although several studies have shown that saikosaponins exert anti-cancer activity in several cancer cell lines, the effect of combining saikosaponins with chemotherapeutic drugs has never been addressed. In the present study, we found that both SSa and SSd, Androgen Receptor Antagonist price two major triterpene saponins could sensitize a number types of human cancer cells to cisplatin-induced cell death. Importantly, we found that the chemosensitization effect of saikosaponin is mainly mediated by the induction of cellular reactive oxygen species (ROS) accumulation in cancer cells. To our knowledge, this is the first report showing that saikosaponin-induced cellular ROS accumulation mediates synergistic cytotoxicity in saikosaponins and cisplatin co-treated cancer cells. These results suggest that saikosaponins are good adjuvant agents for sensitizing cancer cells to cisplatin, highlighting that the combination of saikosaponins and cisplatin could be an effective therapeutic strategy for improving the anticancer value

Tubastatin A cost of cisplatin. Materials and methods Reagents Orotidine 5′-phosphate decarboxylase Saikosaponin-a and -d were purchased from Chinese National Institute of the Control Pharmaceutical and Biological Products (Beijing, China). Cisplatin, Butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) were from Sigma (St. Louis, MO, USA). The pan-caspase inhibitor zVAD-fmk was purchased from Calbiochem (La Jolla, CA, USA). Antibodies against active caspase-3, poly (ADP-ribose) polymerase (PARP) were purchased from BD bioscience (San Diego, CA, USA). Anti-β-actin was purchased from Protein Tech (Chicago, IL, USA). 5-(and -6)-chloromethyl-2′, 7′-dichlorodihydro-fluorescein diacetate acetyl ester (CM-H2DCFDA) and dihydroethidium (DHE) were purchased from Molecular Probes (Eugene, OR, USA). Cell

culture Two cervical cancer cell lines HeLa and Siha, an ovarian cancer cell line SKOV3, and a non-small cell lung cancer cell line A549 were from American Type Culture Collection (ATCC, Manassas, VA, USA) and grown in RPMI 1640 or DMEM supplemented with 10% fetal bovine serum (Hyclone, Thermo Scientific, Beijing, China), 1mmol/L glutamate, 100 units/mL penicillin, and 100 μg/mL streptomycin under standard incubator condition (37°C, 5% CO2). Cell death assay Cells were seeded in 96-well plate one day before treatment and then treated as indicated in each figure legend. Cell death was assessed based on release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit (Promega, Madison, WI, USA) as described previously [20].