RESUMO
Inflammation is the major symptom of the innate immune response to microbial infection. Macrophages, immune response-related cells, play a role in the inflammatory response. Galangin is a member of the flavonols and is found in Alpinia officinarum, galangal root and propolis. Previous studies have demonstrated that galangin has antioxidant, anticancer, and antineoplastic activities. However, the anti-inflammatory effects of galangin are still unknown. In this study, we investigated the anti-inflammatory effects of galangin on RAW 264.7 murine macrophages. Galagin was not cytotoxic to RAW 264.7 cells, and nitric oxide (NO) production induced by lipopolysaccharide (LPS)-stimulated macrophages was significantly decreased by the addition of 50 µM galangin. Moreover, galangin treatment reduced mRNA levels of cytokines, including IL-1ß and IL-6, and proinflammatory genes, such as iNOS in LPS-activated macrophages in a dose-dependent manner. Galangin treatment also decreased the protein expression levels of iNOS in activated macrophages. Galangin was found to elicit anti-inflammatory effects by inhibiting ERK and NF-κB-p65 phosphorylation. In addition, galangin-inhibited IL-1ß production in LPS-activated macrophages. These results suggest that galangin elicits anti-inflammatory effects on LPS-activated macrophages via the inhibition of ERK, NF-κB-p65 and proinflammatory gene expression.
Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Animais , Anti-Inflamatórios/efeitos adversos , Western Blotting , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , MAP Quinases Reguladas por Sinal Extracelular/imunologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/efeitos adversos , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos/enzimologia , Macrófagos/imunologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Óxido Nítrico/imunologia , Fosforilação , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição RelA/imunologiaRESUMO
Myricetin is a flavonol found in various berries, herbs, and walnuts. Previous studies have demonstrated that myricetin has anticancer effects against several types of cancer, including hepatocarcinoma, skin carcinoma, and pancreatic cancer. However, the anticancer activity of myricetin on human colon cancer has not been yet established. In the present study, we investigated the anticancer effects of myricetin on HCT-15 human colon cancer cells. We found that myricetin induces cytotoxicity and DNA condensation in human colon cancer cells in a dose-dependent manner. We also determined that myricetin increases the BCL2-associated X protein/B-cell lymphoma 2 ratio, but not cleavage of caspase-3 and -9. In addition, myricetin induced the release of apoptosis-inducing factor from mitochondria. These results suggest that myricetin induces apoptosis of HCT-15 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Flavonoides/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Fator de Indução de Apoptose/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , DNA de Neoplasias/metabolismo , Humanos , Transdução de Sinais , Proteína Killer-Antagonista Homóloga a bcl-2/biossínteseRESUMO
Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Flavonoides/farmacologia , Mitocôndrias/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Citoplasma/metabolismo , Feminino , Flavonoides/química , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Transdução de SinaisRESUMO
18ß-Glycyrrhetinic acid (ß-GA) is a natural triterpenoid compound derived from licorice root. ß-GA has been demonstrated to exert antiviral and antitumor effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DCs) remain to be clearly elucidated. In this study, we attempted to determine whether ß-GA could influence DCs surface molecule expression, antigen uptake capacity, cytokine production and capacity to induce T-cell differentiation. The DCs used in this study were derived from murine bone marrow cells, and were used as immature or lipopolysaccharide (LPS)-stimulated mature DCs. The DCs were then assessed with regard to surface molecules expression, cytokine production, capacity to induce T-cell differentiation and proliferation. ß-GA was shown to significantly suppress the expression of surface molecules CD80, CD86, major histocompatibility complex (MHC) class I and MHC class II as well as the levels of interleukin-12 production in LPS-stimulated DCs. Moreover, ß-GA-treated DCs showed an impaired induction of the T helper type 1 immune response. These findings provide important understanding of the immunopharmacological functions of ß-GA and have ramifications for the development of therapeutic adjuvants for the treatment of DCs-related acute and chronic diseases.