ABSTRACT
Genome-wide gene expression profiling of cancers has consistently identified the FOXM1 as one of the most commonly upregulated genes in cancer cells that plays an essential role in the regulation of a wide spectrum of biological processes, including inhibition of apoptosis. Since the anticancer activity of EUG reported in the literature is related to induction of apoptosis in cancer cells, we hypothesized that there is a correlation between the EUG-induced apoptosis effect and downregulation of FOXM1. A series of experiments were conducted to evaluate the effect of EUG on cellular viability of cancer cells (MTT) and its potential regulatory effect on FOXM1 protein levels (western blots). Our findings confirm the anticancer effect of EUG on different human cancer cell lines as previously reported in the literature (SKBR3 LC50: 318.6; HT29 LC50: 525.5; and HepG2 LC50: 2090.0 µM). However, we demonstrated that EUG does not regulate the FOXM1. The results evidenced the anticancer effect of EUG on three cancer cell lines and showed that the EUG- apoptosis induced effect is not related to regulation of FOXM1 at the protein level. Further studies must be done to provide information on the mechanism of action of this agent.
Estudos do genoma de células tumorais identificaram o FOXM1 como o fator de transcrição mais expresso, desempenhando papel essencial em uma gama de processos biológicos, incluindo a inibição da apoptose celular. A atividade anticarcinogênica do EUG, relatada na literatura, está relacionada à indução de apoptose em células cancerosas, por isso geramos a hipótese de que pode existir correlação entre este efeito indutor de apoptose e a supressão do FOXM1. Um conjunto de experimentos foi realizado com o objetivo de avaliar o efeito do EUG na viabilidade celular (MTT) e o potencial regulatório sobre o nível de proteínas do FOXM1, em células cancerosas (western blots). Nossos resultados corroboram o efeito anticancerígeno do EUG relatado na literatura em diferentes linhagens celulares (SKBR3 LC50: 318.6; HT29 LC50: 525.5; e HepG2 LC50: 2090.0 µM). Entretanto ficou demonstrado que o EUG não interfere no nível proteico do FOXM1. Em nosso estudo demonstramos o efeito citotóxico do EUG em três linhagens celulares de câncer, sendo evidenciado que o efeito indutor de apoptose promovido pelo mesmo não é dependente da regulação do fator de transcrição FOXM1. Estudos mais detalhados serão conduzidos no intuito de esclarecer os mecanismos de ação desde agente anticarcinogênico.
Subject(s)
Oils, Volatile , Apoptosis , Syzygium , Cytotoxicity, ImmunologicABSTRACT
Aims: Liver diseases have become one of the major causes of morbidity and mortality all over the world. This study investigated the hepatoprotective and antioxidant effect of rosemary essential oil (REO) and ginger essential oil (GEO), against paracetamol-induced liver damage. Methodology: The hepatoprotective effects of REO and GEO at doses of 125, 250 and 500 mg/kg, respectively, orally for 7 days were determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity. In vitro antioxidant activity of REO and GEO were evaluated by assessing the free radical 2, 2-diphenyl-1- picrylhydrazyl (DPPH•)-scavenging activity and lipid peroxidation. Results: REO and GEO reduced the levels of the serum marker enzymes AST, ALT, and MPO activity. The essentials oils also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. Conclusion: These results suggest that REO and GEO have hepatoprotective effects on acetaminophen-induced hepatic damage in mice probably due to their antioxidant effect.