RESUMO
Gastric cancer is one of the most lethal cancers with unmet clinical treatment and low 5-year survival rate. Schisantherin A is a major compound derived from Fructusschisandrae while its anti-tumor role remains nearly unknown. Here, we reported that schisantherin A had an anti-proliferation effect on gastric cancer cell lines MKN45 and SGC-7901. Schisantherin A induced cell cycle arrest at G2/M phase and cell apoptosis, and inhibited cell migration in gastric cancer MKN45 and SGC7901 cells. Meanwhile, upregulation of cleaved caspase-9, cleaved caspase-3 and cleaved PARP were accompanied with the loss of mitochondrial membrane potential (MMP). Moreover, schisantherin A induced ROS-dependent JNK phosphorylation with higher ROS production. The JNK inhibitor and ROS scavenger NAC rescued the cell apoptosis and cycle inhibition elicited by schisantherin A. Furthermore, the expression level of antioxidant factor Nrf2 was suppressed by schisantherin A. These findings suggest that schisantherin A possesses an anti-tumor activity via activation of ROS/JNK with Nrf2 inhibition, indicating that schisantherin A is a promising chemotherapeutic candidate for gastric cancer.
Assuntos
Apoptose/efeitos dos fármacos , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Lignanas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ciclo-Octanos/química , Dioxóis/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Lignanas/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Schisandra/química , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Gastric cancer is a common malignant tumor with high morbidity and mortality worldwide, which seriously affects human health. Gramicidin is a short peptide antibiotic which could be used for treating infection induced by bacteria or fungi. However, the anti-cancer effect of gramicidin on gastric cancer cells and its underlying mechanism remains largely unknown. RESULTS: Gastric cancer cells SGC-7901, BGC-823 and normal gastric mucosal cells GES-1 were treated with different concentrations of gramicidin respectively. The results of CCK-8 experiment revealed cellular toxicity of gramicidin to cancer cells while cell colony formation assay showed that gramicidin significantly inhibited the proliferation of gastric cancer cells, but had little effect on normal gastric mucosal cells. In addition, the wound healing assay showed that gramicidin inhibited the migration of SGC-7901 cell. Meanwhile, apoptosis and cell cycle analysis revealed that gramicidin induced cell apoptosis with G2/M cell cycle inhibition. Furthermore, western blot analysis demonstrated that gramicidin down-regulated the expression of cyclinD1 and Bcl-2 as well as the FoxO1 phosphorylation. CONCLUSIONS: The current study illustrated the anti-tumor activity of gramicidin on gastric cancer cells, providing a possibility for gramicidin to be applied in clinical practice for the treatment of gastric cancer.
Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Gramicidina/farmacologia , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Ciclina D1/efeitos dos fármacos , Ciclina D1/metabolismo , Regulação para Baixo , Proteína Forkhead Box O1/efeitos dos fármacos , Proteína Forkhead Box O1/metabolismo , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
BACKGROUND: Gastric cancer is a common malignant tumor with high morbidity and mortality worldwide, which seriously affects human health. Gramicidin is a short peptide antibiotic which could be used for treating infection induced by bacteria or fungi. However, the anti-cancer effect of gramicidin on gastric cancer cells and its underlying mechanism remains largely unknown. RESULTS: Gastric cancer cells SGC-7901, BGC-823 and normal gastric mucosal cells GES-1 were treated with different concentrations of gramicidin respectively. The results of CCK-8 experiment revealed cellular toxicity of gramicidin to cancer cells while cell colony formation assay showed that gramicidin significantly inhibited the proliferation of gastric cancer cells, but had little effect on normal gastric mucosal cells. In addition, the wound healing assay showed that gramicidin inhibited the migration of SGC-7901 cell. Meanwhile, apoptosis and cell cycle analysis revealed that gramicidin induced cell apoptosis with G2/M cell cycle inhibition. Furthermore, western blot analysis demonstrated that gramicidin down-regulated the expression of cyclinD1 and Bcl-2 as well as the FoxO1 phosphorylation. CONCLUSIONS: The current study illustrated the anti-tumor activity of gramicidin on gastric cancer cells, providing a possibility for gramicidin to be applied in clinical practice for the treatment of gastric cancer.
