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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2010.tde-28092010-111234
Document
Author
Full name
Evandro Luís de Oliveira Niero
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Santelli, Glaucia Maria Machado (President)
Ionta, Marisa
Jaeger, Ruy Gastaldoni
Mori, Lyria
Ribeiro, Alberto Augusto Gonçalves de Freitas Castro
Title in Portuguese
Efeitos de ácido cinâmico sobre melanócitos e células derivadas de melanomas humanos: avaliação do seu potencial antitumoral e de proteção contra danos celulares causados por radiação ultravioleta.
Keywords in Portuguese
Aberrações nucleares
Ácido cinâmico
Apoptose
Ciclo celular
Citoesqueleto
Cultura de células
Melanoma (Humano)
Abstract in Portuguese
Poucos tratamentos têm efeito sobre melanomas metastáticos, mas novas drogas vêm sendo estudadas para combater esta doença. Este trabalho avaliou efeito de ácido cinâmico (AC) em melanócitos (NGM) e células de melanoma (HT144) sobre alterações no ciclo, morte, comunicação e mobilidade celular e morfologia nuclear e investigou efeito de proteção à radiação ultravioleta (UV). AC inibiu crescimento de HT144 em relação a NGM. Essa inibição deve ocorrer devido a dano no DNA que levou à inibição da fase S, formação de aberrações nucleares e indução de morte. AC induziu formação de micronúcleos nas células NGM. O citoesqueleto foi reorganizado após AC o que diminuiu a mobilidade celular. Apesar de não induzir comunicação entre as células HT144 o AC aumentou níveis citoplasmáticos de cx43 em células de hepatocarcinoma, o que contribui para a morte celular. Isto sugere maior citotoxicidade de AC em células HT144 em comparação com NGM. Porém, AC não protegeu as células dos efeitos de UV e sua genotoxicidade em células NGM indica que sua atividade depende de mais estudos.
Title in English
Cinnamic acid effects on cultured human melanocytes and melanoma derived cells: evaluation of its antitumor potential and protection against cell damage caused by ultraviolet radiation.
Keywords in English
Apoptosis
Cell culture
Cell cycle
Cinnamic acid
Cytoskeleton
Melanoma (Human)
Nuclear aberrations
Abstract in English
Consumption of vegetables could decrease the risk of malignancies. Cinnamic acid (CA), commonly found in plants have been studied because their antitumor activitie. The present work aimed to evaluate effect of CA in melanocytes (NGM) and melanoma cells (HT-144) by focusing the cell cycle, death, mobility and communication and formation of nuclear aberration and to investigate potential of protection against UV radiation. CA inhibited cell growth of melanoma cells compared to melanocytes, probably due to DNA damage leading to DNA synthesis inhibition, induction of nuclear aberrations and apoptosis. High concentration of CA induced micronuclei in NGM cells. We observed cytoskeleton reorganization that decreased cell mobility in both cells. We have not observed communication in HT144 after treatment, but CA increased expression of cx43 in hepatocarcinoma cells, probably leading to apoptosis. CA did not showed protection effects against ultraviolet radiation and its genotoxic effects in NGM cells indicates that its mechanism of action must be further investigated.
 
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Publishing Date
2010-10-20
 
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