title: Effect of natural and synthetic estrogens on a549 lung cancer cells: correlation of chemical structures with cytotoxic effects.
abstract: A series of synthetic (nonylphenol, diethylstilbestrol, and bisphenol A) and natural (quercetin, resveratrol, and genistein) phenolic estrogens were investigated for their ability to affect the viability and proliferation of A549 lung cancer cells. To assess and distinguish the cytotoxic effect of individual estrogens, we used both the MTT tetrazolium spectrophotometric method and the fluorescence assay, while the induction of the cell specific apoptotic process was examined by fluorescence microscopy after treatment of cells with SYTO 24 green fluorescent dye. A systematic study of interferences for both fluorescence and MTT methods is presented. The results showed that both natural and synthetic estrogens decreased the viability and proliferation of A549 lung cancer cells in a dose-dependent manner but at different sensitivities. Nonylphenol appeared very different as compared to the other estrogens, acting by inducing the higher inactivation rate of the cells within a very short time. The cytotoxic effect of the estrogens was directly related to their structural and conformational characteristics including chain length, number, and position of hydroxyl groups and degree of saturation.
authors.affiliation: Department of Chemistry, State University of New York-Binghamton, P.O. Box 6000, Binghamton, New York 13902, USA.
authors.forename: Silvana
authors.initials: S
authors.lastname: Andreescu
authors.forename: Omowunmi A
authors.initials: OA
authors.lastname: Sadik
authors.forename: Dennis W
authors.initials: DW
authors.lastname: McGee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D045166:Estradiol Congeners / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D005453:Fluorescence; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000737:chemistry / Q000145:classification / Q000633:toxicity; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004273:DNA, Neoplasm; D045166:Estradiol Congeners; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D013778:Tetrazolium Salts; D013844:Thiazoles; C025256:nonylphenol; C022616:thiazolyl blue