Cynaropicrin Potentiates the Anti-Tumor Effects of Paclitaxel and 5-Fluorouracil on KYSE30 Human Esophageal Carcinoma
Abstract Natural products or their use in combination therapy regimens may reduce side effects of chemotherapy and increase the effectiveness of treatments. The cytotoxic effects of cynaropicrin, a sesquiterpene lactone isolated from Centaurea behen were evaluated for the first time against esophageal squamous carcinoma cells (KYSE30). The synergistic effects of cynaropicrin with paclitaxel and 5-fluorouracil (5-Fu), conventional chemotherapeutic drugs used for esophageal cancer treatment, were also investigated. MTT results indicated that the 50% inhibitory concentration (IC50) values of cynaropicrin on KYSE30 cells after 24, 48 and 72 h were 72, 43 and 28 μM, respectively, which were significantly different from those on normal HDF cells. It was also determined that cynaropicrin could induce the cell death via apoptosis. Our results indicated that cynaropicrin had synergism with both drugs. The best effects of cynaropicrin in combination with paclitaxel were observed at 48 h, in which dose reduction of paclitaxel reached 3 times in IC50. Combination with 5-fluorouracil, resulted in 15 times dose reduction of 5-Fu in IC50 at 24 h. In conclusion cynaropicrin has selective cytotoxic effects on KYSE30 cells and we suggest its use in combination therapies with paclitaxel and 5-Fu, which would reduce the side effects of these conventional treatments.
