title: Retinoids and citral modulated cell viability, metabolic stability, cell cycle progression and distribution in the a549 lung carcinoma cell line - biomed 2010.
abstract: Lung cancer is the second leading deadly cancer in United States. In 2007, the United States reported 213,380 new lung cancer diagnoses and 160,390 deaths caused by lung cancer. Retinoic acid and retinyl esters are the oxidized and storage forms of vitamin A in the body. At low levels, they maintain many functions as hormones affecting vision, bone growth, reproduction, cellular division, and differentiation. Recent publications have found retinoid receptors to be effective therapeutic targets in some cancer cell lines and that retinoids were functional cell modulators of the RAR/RXR nuclear hormone receptors that may impact the development of lung cancer. We hypothesize that retinoic acid and retinyl esters will negatively impact the A549 lung carcinoma cell line model in vitro and that exposure to higher concentrations of retinoids will induce impairments indicative of metabolic implications seen in chronic conditions such as cancer. Citrals are specific inhibitors of retinoid metabolism and are employed to ascertain the specificity of retinoid impacts on the cell model. The aim of this study was to expose the A549 cell line model to various concentrations of retinoic acid, and Citrals (0-160 g/ml). Growth patterns of exposed cells were screened during time intervals ranging from 24-72 hours. The effects were measured through phase microscopy, cell proliferation MTT assay, FACS analysis for cell cycle parameters and western blot analyses for cyclins. Data generated from phase contrast microscopy and MTT assays showed an increased physical destruction, metabolic impairment and a decrease in the viability of A549 cell line model after 72 hours of exposure to retinoic acids and. Observations on the effects exhibited with Citrals (cis and trans vs. diethyl acetal) suggests the reversal of retinoid toxicity and a decrease in cell metabolic as well as physical destructions and positive cell proliferation. Results from FACS analysis showed modulation in the cell cycle distribution/progression upon exposure to retinoids and that Citrals did reverse these effects in the cell line model. Western blot analysis confirmed the findings obtained from testing parameters. We conclude that modulation of metabolic integrity, cell cycle distribution and cell survival through retinoids/citrals in the lung carcinoma model is promising and warrants further therapeutic investigation.
authors.affiliation: University of Mississippi Medical Center, MS.
authors.forename: Ibrahim O
authors.initials: IO
authors.lastname: Farah
authors.forename: Quannesha
authors.initials: Q
authors.lastname: Trimble
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ndebele
authors.forename: Anthony
authors.initials: A
authors.lastname: Mawson