In Vitro Synergistic Interaction between DTA0100 and Radiation in Human Cancer Cell Lines

Elisa      Bordon; Leticia      G. Leon; Carla      Rios-Luci; Pedro      C. Lara; Jose      M. Padron

Abstract

DTA0100 is a new catalytic inhibitor of the human DNA topoisomerase IIα that induces G2/M phase cell cycle arrest in human solid tumor cells lines from various malignancies. In our study, we investigated the effectiveness of the combined treatment of ionizing radiation with DTA0100 on the survival of three representative human solid tumor cell lines: HeLa (cervix), WiDr (colon) and SW1573 (non-small cell lung cancer). The concomitant treatment of DTA0100 and irradiation showed a synergistic and antagonistic effect in the three cell lines tested. A synergistic cytotoxic effect of the combination of DTA0100 and radiation was confirmed by the median drug effect analysis method. It was found that in those protocols where the drug was administered after radiation the most synergistic effect was achieved. Our study constitutes the first in vitro evidence for synergistic effects between DTA0100 and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with cervical, colon and non-small cell lung cancer cells.

Keywords: Anticancer drugs, Antiproliferative, Cancer, Catalytic inhibitor, Cell lines, Chemoradiotherapy, Chemotherapy, DNA, Drug combinations, Mechanism of action, Median drug effect, Mitosis, Radiation therapy, Screening, Topoisomerase