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Evaluation of Arsenic Trioxide Potential for Lung Cancer Treatment: ASSessment of Apoptotic Mechanisms and Oxidative Damage

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@ Clark Atlanta University

Walker, Alice M Stevens, Jacqueline J Ndebele, Kenneth Tchounwou, Paul B

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Abstract: Background: Lung cancer is one of the most lethal and common cancers in the world, causing up to 3 million deaths annually. The chemotherapeutic drugs that have been used in treating lung cancer include cisplatinpemetrexed, cisplastin-gencitabinoe, carboplatin-pacitaxel and crizotinib. Arsenic trioxide (ATO) has been used in the treatment of acute promyelocytic leukemia. However, its effects on lung cancer are not known. We hypothesize that ATO may also have a bioactivity against lung cancer, and its mechanisms of action may involve apoptosis, DNA damage and changes in stress-related proteins in lung cancer cells. Methods: To test the above stated hypothesis, lung carcinoma (A549) cells were used as the test model. The effects of ATO were examined by performing 6-diamidine-2 phenylindole (DAPI) nuclear staining for morphological characterization of apoptosis, flow cytometry analysis for early apoptosis, and western blot analysis for stressrelated proteins (Hsp70 and cfos) and apoptotic protein expressions. Also, the single cell gel electrophoresis (Comet) assay was used to evaluate the genotoxic effect. Results: ATO-induced apoptosis was evidenced by chromatin condensation and formation of apoptotic bodies as revealed by DAPI nuclear staining. Cell shrinkage and membrane blebbing were observed at 4 and 6 ug/ml of ATO. Data from the western blot analysis revealed a significant dose-dependent increase (p less than 0.05) in the Hisp 70, caspase 3 and p53 protein expression, and a significant (p less than 0.05) decrease in the cfos, and bol-2 protein expression at 4 and 6 g/ml of ATO. There was a slight decrease in cytochrome...

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Clark Atlanta University

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Digital Library of Georgia