RESUMO
OBJECTIVE: Aqueous extract from the leaves of Toona sinensis Roem. has been shown to have an anti-proliferative effect on human lung cancer cells. In this study, we analyzed the anti-cancer activity/effect of different extraction fractions of the extract from T. sinensis leaves on ovarian cancer cells. METHODS: Cell viability was determined by XTT cell proliferation assay and cell survival assay. Apoptotic effect was detected by morphological analysis and immunoblotting. Cell cycle effect was evaluated by flow cytometry analysis and immunoblotting. In vivo therapeutic effect was evaluated by the subcutaneous inoculation of SKOV3 cells in nude mice (Foxnlnu/Foxnlnu) model. RESULTS: TSL2 of T. sinensis was more cytotoxic than other fractions and exhibited selectivity for ovarian cancer cell lines. TSL2 arrested SKOV3 ovarian cancer cells at the G2/M phase and induced cancer cells go through apoptotic pathway. Ex vivo xenograft study of nude mice showed that intraperitoneal injection of TSL2 was able to suppress the proliferation of ovarian cancer cells without significant nephrotoxicity, liver toxicity, or bone marrow suppression.
Assuntos
Cedrela/química , Neoplasias Ovarianas/tratamento farmacológico , Extratos Vegetais/farmacologia , Árvores/química , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Annonaceous acetogenins are a group of potential anti-neoplastic agents isolated from Annonaceae plants. We purified squamocin, a cytotoxic bis-tetrahydrofuran acetogenin, from the seeds of Annona reticulata and analyzed its biologic effects on cancer cells. We showed that squamocin was cytotoxic to all the cancer lines tested. Furthermore, squamocin arrested T24 bladder cancer cells at the G1 phase and caused a selective cytotoxicity on S-phase-enriched T24 cells. It induced the expression of Bax and Bad pro-apoptotic genes, enhanced caspase-3 activity, cleaved the functional protein of PARP and caused cell apoptosis. These results suggest that squamocin is a potentially promising anticancer compound.