Abstract 3455: Arsenic trioxide modulates DNA synthesis and apoptosis in lung carcinoma cells

Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows the cancer cells growth. Although it has been reported that arsenic acts on cells by influencing numerous signal transduction pathways, cell cycle progression, and/or apoptosis, its apoptotic mechanisms are very complex. The primary objective of this research is to evaluate the effects of arsenic trioxide on DNA synthesis and to determine whether arsenic induced-apoptosis is mediated via caspase activation, p38 mitogen-activated protein kinase (MAPK), and cell cycle arrest. To achieve this goal, the lung cancer (A549) cells were cultured following standard protocol, and exposed to various doses (0, 2, 4, and 6 µg/ml) of arsenic trioxide for 48 h. The effect of arsenic trioxide on DNA synthesis was determined by [ 3 H]thymidine incorporation assay. Apoptosis was determined by caspase-3 fluorescein isothiocyanate (FITC) assay, and immunoblot analysis (p38 MAP kinase activity). The cell cycle analysis was evaluated propidium iodide assay. [ 3 H]Thymidine incorporation assay revealed dose-related cytotoxic response at higher levels of exposure. Our findings revealed that arsenic trioxide modulated caspase 3 activity and induced p38 map kinase activation in lung carcinoma (A549) cells. The data revealed no cell cycle arrest at the sub-G 0 in A549 cells when treated with arsenic trioxide. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3455.