Melatonina reduz o crescimento tumoral do câncer colo-retal – células Caco-2 Ultrastructural aspects of melatonin cytotoxicity on Caco-2 cells in vitro. Batista AP1, da Silva TG2, Teixeira AA3, de Medeiros PL4, Teixeira VW 1, Alves LC5, Dos Santos FA5, Silva EC4. Micron. 2014 Apr;59:17-23. doi: 10.1016/j.micron.2013.12.003. Epub 2013 Dec 26. Author information 1 Department of Animal Morphology and Physiology, University Federal Rural of Pernambuco, Rua Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil. 2 Department of Antibiotics, University Federal Rural of Pernambuco, Av. Prof. Moraes Rego, 1235, 50670-901 Recife, PE, Brazil. 3 Department of Animal Morphology and Physiology, University Federal Rural of Pernambuco, Rua Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil. Electronic address: [email protected]. 4 Department of Histology and Embryology, University Federal Rural of Pernambuco, Av. Prof. Moraes Rego, 1235, 50670-901 Recife, PE, Brazil. 5 Laboratory of Immunopathology Keizo Asami (LIKA), and Research Center Aggeu Magalhães, CPqAM/Fiocruz, University Federal of Pernambuco, Av. Prof. Moraes Rego, 1235, 50670-901 Recife, PE, Brazil. Abstract Colon adenocarcinoma is a disease expanding worldwide. Cancer of colon and rectum are among the top ten most insidious types in Brazil. In vitro and in vivo studies have demonstrated the efficacy of the hormone melatonin to prevent and reduce tumor growth. However, there are only few studies addressing the action of melatonin on Caco-2 cells. Thus, the cytotoxic effect of melatonin on the ultrastructure of Caco-2 cells was investigated. The MTT colorimetric method was used to assess the cytotoxicity. A total of 2×10(6)cells/mL were seeded in microplates and incubated at 50, 25, 12.5, 6.25, 3.125, 1.56, 0.78 and 0.0 (control) μg/mL of melatonin. For ultrastructural analysis concentrations with low, medium and high cytotoxicity plus the control were used for ultrastructural analysis. The concentrations 50, 1.56 and 0.78 μg/mL of melatonin showed low, medium and high cytotoxicity, respectively. Ultrastructurally, the control tumor cells were shown to be preserved. Caco-2 cells showed morphological changes at 50 μg/mL of melatonin, with numerous vacuoles, mitochondrial degeneration and reduced glycogen. However, Caco-2 cells also showed altered morphology in treatments at 1.56 and 0.78 μg/mL of melatonin with characteristics of cells in degeneration by the presence of numerous vacuoles, absence of microvilli, mitochondrial degeneration and nuclear fragmentation. Thus, one can infer that concentrations of 1.56 and 0.78 μg/mL of melatonin promote cytotoxicity in Caco-2 cells, which can probably be related to the generation of reactive oxygen species (ROS). Copyright © 2013 Elsevier Ltd. All rights reserved. KEYWORDS: Adenocarcinoma, Caco-2, Cytotoxicity, Melatonin, Ultrastructure PMID:24530360