RESUMO
In the report, three bioactive fractions from Cerrena unicolor: laccase (LAC), endopolysaccharides (c-EPL), and low molecular weight (ex-LMS) were tested for the first time towards their antiviral, immunostimulatory, cytotoxic and antiproliferative effect. The immunomodulatory activity was studied by means of THP-1-derived macrophages able to synthesize and secrete IL-6 and TNF-α. We used cervical carcinoma cell lines SiHa (ATCC, HTB-35) and CaSki (ATCC, CRL 1550) to determine antitumor activity and human skin fibroblasts (HSF) as a control. SiHa and L929 cell lines were used in the antiviral activity assay to propagate HHV-1 and EMCV, respectively. LAC was the most active against HSV at an early stage of viral replication, whereas the activity of laccase against EMCV was evident after incubation of the virus with LAC before and after the adsorption step. Moreover, the investigations showed that the fungal c-EPL fraction stimulated the production and secretion of TNF-α and IL-6 by THP-1-derived macrophages up to a level of 2000 pg/ml and 400 pg/ml, respectively. It was indicated for the first time that the LAC and ex-LMS fractions exhibited anticancer activity. This resulted from their cytotoxic or antiproliferative action against the investigated tumor cells at concentrations above 250 µg/ml and 10 µg/ml, respectively.
Assuntos
Antineoplásicos/isolamento & purificação , Antivirais/isolamento & purificação , Polissacarídeos Fúngicos/isolamento & purificação , Proteínas Fúngicas/isolamento & purificação , Fatores Imunológicos/isolamento & purificação , Lacase/isolamento & purificação , Polyporaceae/química , Antineoplásicos/farmacologia , Antivirais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Vírus da Encefalomiocardite/efeitos dos fármacos , Vírus da Encefalomiocardite/fisiologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibroblastos/virologia , Polissacarídeos Fúngicos/farmacologia , Proteínas Fúngicas/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Humanos , Fatores Imunológicos/farmacologia , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Lacase/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Macrófagos/virologia , Polyporaceae/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
A new exopolysaccharide preparation isolated from stationary cultures of the white rot fungus Ganoderma applanatum (GpEPS) was tested in terms of its bioactive properties including its cytotoxic and immunostimulatory effect. The results indicate that the tested GpEPS (at concentrations above 22.85 µg/mL and 228.5 µg/mL) may exhibit selective activity against tumor cells (cell lines SiHa) and stimulate production of TNF-α THP-1-derived macrophages at the level of 752.17 pg/mL. The GpEPS showed antibacterial properties against Staphyloccoccus aureus and a toxic effect against Vibrio fischeri cells (82.8% cell damage). High cholesterol-binding capacity and triglycerides-binding capacity (57.9% and 41.6% after 24 h of incubation with the tested substances, resp.) were also detected for the investigated samples of GpEPS.