RESUMO
In the present study, we examined the effects of methanol extracts of Picrasma quassioides (MEPQ) on apoptosis in human cervical cancer cells. The results showed that MEPQ decreased the viability and induced caspase-dependent apoptosis in HEp-2 cells. MEPQ decreased specificity protein 1 (Sp1) in HEp-2 cells, whereas Sp1 mRNA was not changed. We found that MEPQ reduced Sp1 protein through proteasome-dependent protein degradation, but not the inhibition of protein synthesis. Also, MEPQ increased the expressions of Bad and truncated Bid (t-Bid) but did not alter other Bcl-2 family members. The knock-down of Sp1 by both Sp1 interfering RNA and Mithramycin A, Sp1 specific inhibitor clearly increased Bad and t-Bid expression to decrease cell viability and induce apoptosis. In addition, MEPQ inhibited cell viability and induced apoptotic cell death through the modulation of Sp1 in KB cells. These results suggest that MEPQ may be a potential anticancer agent for human cervical cancer.
Assuntos
Apoptose/efeitos dos fármacos , Picrasma , Extratos Vegetais/farmacologia , Fator de Transcrição Sp1/metabolismo , Neoplasias do Colo do Útero/metabolismo , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Metanol , Plicamicina/análogos & derivados , Plicamicina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Interferente Pequeno/genética , Solventes , Fator de Transcrição Sp1/genética , Neoplasias do Colo do Útero/patologia , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
Fucoidan is a sulfated polysaccharide present in brown algae that has been identified to exhibit multiple biological effects. In this study, the apoptotic effects of fucoidan in MC3 human mucoepidermoid carcinoma (MEC) cells were investigated. The apoptotic effects of fucoidan on MC3 MEC cells were evaluated by cell proliferation assay, 4',6-diamidino-2-phenylindole staining and western blot analysis. The results showed that fucoidan decreased cell proliferation and induced caspase-dependent apoptosis in MC3 MEC cells. Fucoidan downregulated the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, whereas phospho-p38 mitogen-activated protein kinase or phospho-c-Jun NH2-terminal kinase (JNK) levels were not altered. In addition, fucoidan significantly decreased the expression levels of myeloid cell leukemia-1 (Mcl-1). These results suggest that fucoidan is able to modulate the ERK1/2 pathway and thereby regulate Mcl-1 protein expression and induce apoptosis in MC3 MEC cells. Therefore, fucoidan may be a promising agent for the treatment of human MEC.