title: Diverse sensitivity of cells representing various stages of colon carcinogenesis to increased extracellular zinc: implications for zinc chemoprevention.
abstract: The relationship between zinc intake and risk of colon cancer is widely recognized. Despite reported mechanisms of zinc-mediated effects in colonic cells no information is available on whether zinc is capable of inducing cell death of malignant colonocytes. The present study shows that increased external zinc concentrations inhibit cell growth of three different colon cancer cell lines representing different stages of colon cancer: HCT-116, HT-29 and SW620 cells and induce their death. Of the tested cell lines, SW620 cells proved to be the most sensitive to externally added zinc and this sensitivity was at least partly due to increased levels of intracellular free zinc and the inability to overexpress metallothionein. Further studies into the mechanisms of zinc-induced cell injury and cell death revealed oxidative stress as the most important underlying mechanism activating stress kinase-dependent signaling, perturbation of mitochondria and plasma membrane damage. In addition, observed cell death in individual cell populations was cell line-dependent and variable including cells displaying features of apoptosis, necrosis, autophagy and other mixed-types. In conclusion, presented results for the first time show variability of responses to zinc in colon cancer at different stages as modeled in vitro and suggest that zinc-induced cell death despite common underlying mechanism(s) might have a variable nature.
authors.affiliation: Department of Medical Biology and Genetics, Charles University Faculty of Medicine in Hradec Kralove, Simkova 870, 500 38 Hradec Kralove I, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: John
authors.forename: Tomás
authors.initials: T
authors.lastname: Briatka
authors.forename: Emil
authors.initials: E
authors.lastname: Rudolf
mesh_terms: D002277:Carcinoma / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D018890:Chemoprevention / Q000379:methods*; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005110:Extracellular Space / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D009367:Neoplasm Staging; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015032:Zinc