title: Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells.
abstract: Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av, Prof, Lineu Prestes, 1524, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
authors.forename: Evandro Luís de Oliveira
authors.initials: EL
authors.lastname: Niero
authors.forename: Gláucia Maria
authors.initials: GM
authors.lastname: Machado-Santelli
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology* / Q000633:toxicity; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002934:Cinnamates; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C029010:cinnamic acid; D053453:Caspase 9