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Walker AM, Stevens JJ, Ndebele K, et al. Evaluation of Arsenic Trioxide Potential for Lung Cancer Treatment: Assessment of Apoptotic Mechanisms and Oxidative Damage. J Cancer Sci Ther. 2015;8(1):1-9doi: 10.4172/1948-5956.1000379.
Walker, A. M., Stevens, J. J., Ndebele, K., & Tchounwou, P. B. (2016). Evaluation of Arsenic Trioxide Potential for Lung Cancer Treatment: Assessment of Apoptotic Mechanisms and Oxidative Damage. Journal of cancer science & therapy, 8(1), 1-9. https://doi.org/10.4172/1948-5956.1000379
Walker, Alice M, et al. "Evaluation of Arsenic Trioxide Potential for Lung Cancer Treatment: Assessment of Apoptotic Mechanisms and Oxidative Damage." Journal of cancer science & therapy vol. 8,1 (2016): 1-9. doi: https://doi.org/10.4172/1948-5956.1000379
Walker AM, Stevens JJ, Ndebele K, Tchounwou PB. Evaluation of Arsenic Trioxide Potential for Lung Cancer Treatment: Assessment of Apoptotic Mechanisms and Oxidative Damage. J Cancer Sci Ther. 2016 Jan;8(1):1-9. doi: 10.4172/1948-5956.1000379. Epub 2015 Dec 18. PMID: 27158419; PMCID: PMC4856166.
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J Cancer Sci Ther. 2016 Jan;8(1):1-9. doi: 10.4172/1948-5956.1000379. Epub 2015 Dec 18.

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

Journal of cancer science & therapy

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

Affiliations

  1. Molecular and Cellular Biology Research Laboratory, Jackson State University, Jackson, Mississippi, USA.
  2. Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, Jackson, Mississippi, USA.

PMID: 27158419 PMCID: PMC4856166 DOI: 10.4172/1948-5956.1000379

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 cisplatin-pemetrexed, cisplastin-gencitabinoe, carboplatin-paclitaxel 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 stress-related 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 µg/ml of ATO. Data from the western blot analysis revealed a significant dose-dependent increase (p < 0.05) in the Hsp 70, caspase 3 and p53 protein expression, and a significant (p < 0.05) decrease in the cfos, and bcl-2 protein expression at 4 and 6 µg/ml of ATO. There was a slight decrease in cytochrome c protein expression at 4 and 6 µg/ ml of ATO. Comet assay data revealed significant dose-dependent increases in the percentages of DNA damage, Comet tail lengths, and Comet tail moment.

CONCLUSION: Taken together our results indicate that ATO is cytotoxic to lung cancer cells and its bioactivity is associated with oxidative damage, changes in cellular morphology, and apoptosis.

Keywords: A549 cells; Apoptosis; Arsenic trioxide; Genotoxicity; Hsp70; Oxidative stress; bcl-2; c-fos; p53

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