7-Hydroxystaurosporine (UCN-01) Preferentially Sensitizes Cells with a Disrupted TP53 to Gamma Radiation in Lung Cancer Cell Lines

Xiao, H. H., Makeyev, Y., Butler, J., Vikram, B. and Franklin, W. A. 7-Hydroxystaurosporine (UCN-01) Preferentially Sensitizes Cells with a Disrupted TP53 to Gamma Radiation in Lung Cancer Cell Lines. Radiat. Res. 158, 84–93 (2002).Mutations in TP53 occur in more than 50% of the lung cancer patients and are associated with an increased resistance to chemotherapy and radiotherapy. The human lung adenocarcinoma cell lines A549 and LXSN contain a wild-type TP53 and were growth arrested at both the G1- and G2-phase checkpoints after irradiation. However, a TP53-disrupted cell line, E6, was arrested only at the G2-phase checkpoint. UCN-01 (7-hydroxystaurosporine), a CHEK1 inhibitor that abrogates the G2 block, has been reported to enhance radiation toxicity in human lymphoma and colon cancer cell lines. In this study, UCN-01 preferentially enhanced the radiosensitivity of the TP53-disrupted E6 cells compared to the TP53 wild-type cells. This effect was more pronounced in cells synchronized in early G1 phase, where the E6 cells showed a higher resistance to radiation in the absence of drug. These results indicate that the combination of UCN-01 and radiation can more specifically target resistant TP53 mutated cancer cells and spare TP53 wild-type normal cells.