Effects of quinolinone derivative, vesnarinone, in combination with irradiation on human lung cancer cell lines

The quinolinone derivative, vesnarinone, is a novel inotropic agent used in the treatment of heart failure. It has also been found that vesnarinone has a potential anti-cancer activity. To evaluate the anti-cancer activity of vesnarinone in combination with irradiation, we investigated the cytostatic and cytotoxic effects on human lung cancer cell lines (PC-9 and Lu 134A) using MTT assay and isobologram analysis. We also analyzed the nuclear fragmentation of tumor cells by flow cytometric analysis. Our study demonstrated that combination of vesnarinone with irradiation had an additive inhibitory effect on both PC-9 and Lu 134A tumor cell growth. Vesnarinone could improve the sensitivity of tumor cells to irradiation and thus the dose of irradiation could be reduced to half without decreased inhibitory effect. Significant increase of the tumor cell nuclear fragmentation was observed with combination of vesnarinone and irradiation. These results indicate that vesnarinone not only directly inhibited tumor cell growth, but also improved the sensitivity to irradiation. Combination of vesnarinone with irradiation may be an efficacious protocol for lung cancer treatment. The inhibitory effect was ascribed to inducing tumor cell apoptosis.