ABSTRACT
Two new sorbicillinoids, 1 and 2, together with a novel benzofuranone derivative named phialofurone (3), were isolated from a deep-sea sediment-derived fungus, Phialocephala sp. Their structures were established on the basis of spectroscopic data. All compounds displayed cytotoxic effects against P388 (IC(50) values of 11.5±1.4, 0.1±0.1, and 0.2±0.01â µM, resp.) and K562 (IC(50) values of 22.9±0.8, 4.8±0.3 and 22.4±0.9â µM, resp.) cell lines.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Ascomycota/chemistry , Benzofurans/chemistry , Benzofurans/pharmacology , Cyclohexanones/chemistry , Cyclohexanones/pharmacology , Antineoplastic Agents/isolation & purification , Benzofurans/isolation & purification , Cell Line, Tumor , Cell Survival/drug effects , Cyclohexanones/isolation & purification , Drug Screening Assays, Antitumor , Humans , Neoplasms/drug therapyABSTRACT
A new sesquiterpene hydroquinone (1) was isolated from a deep sea sediment derived fungus, Phialocephala sp.. Its structure and stereochemistry were established on the basis of spectroscopic data and optical rotation. This compound was tested for cytotoxicity against P388 (murine leukemia cell) and K562 (human leukemia cell) cell lines, and displayed strong cytotoxic effects with IC50 value of 0.16 and 0.05 micromol x L(-1), separately.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Ascomycota/chemistry , Hydroquinones/chemistry , Hydroquinones/isolation & purification , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Hydroquinones/pharmacology , Inhibitory Concentration 50 , K562 Cells , Leukemia P388/pathology , Mice , Molecular StructureABSTRACT
Semi-vioxanthin isolated from marine-derived fungus was assessed for immunoregulatory activity in mouse RAW264.7 macrophages. In the present study, the facilitative effects of semi-vioxanthin on tumor necrosis factor-alpha (TNF-alpha) and its mRNA expression and on expression of the co-stimulatory molecules, cluster of differentiation (CD) 80, CD86 and major histocompatibility complex class II (MHC II), as well as the molecular mechanism underlying the immunologic enhancement properties of semi-vioxanthin were studied. Our results clearly indicated that semi-vioxanthin treatment resulted in the degradation of IkappaB alpha, which led to the activation and nuclear translocation of the p65 subunit of nuclear factor-kappaB (NF-kappaB), as determined by immunoblotting, immunofluorescence and electrophoretic mobility shift assays (EMSA). Moreover, TNF-alpha production was prevented by NF-kappaB and mitogen-activated protein kinase (MAPK) inhibitors. Inhibition of NF-kappaB and extracellular signal regulated kinases (ERK1/2) activity by specific inhibitors blunted the effect of semi-vioxanthin on the up-regulation of CD80, CD86 and MHCII expression, but neither p38 MAPK nor c-Jun N-terminal kinase (JNK) inhibitor had this effect. Thus, we demonstrate that semi-vioxanthin regulates TNF-alpha production through NF-kappaB and MAPK signaling pathways. Activation of NF-kappaB and ERK1/2 were necessary for CD80, CD86 and MHCII expression induced by semi-vioxanthin. These data suggest that semi-vioxanthin has immunoregulatory effects.
Subject(s)
B7-1 Antigen/genetics , B7-2 Antigen/genetics , Genes, MHC Class II/genetics , Macrophages/physiology , Mitogen-Activated Protein Kinases/physiology , NF-kappa B/physiology , Naphthols/pharmacology , Pyrones/pharmacology , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/genetics , Animals , B7-1 Antigen/biosynthesis , B7-2 Antigen/biosynthesis , Blotting, Western , Cell Line , Electrophoretic Mobility Shift Assay , Flow Cytometry , Fluorescent Antibody Technique , Gene Expression/drug effects , Macrophages/drug effects , Macrophages/metabolism , Mice , Mitogen-Activated Protein Kinases/genetics , NF-kappa B/genetics , Naphthols/isolation & purification , Pyrones/isolation & purification , RNA/biosynthesis , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/biosynthesis , Up-Regulation/drug effectsABSTRACT
Two new compounds, 2, 3, 5-trimethyl-6-(3-oxobutan-2-yl)-4H-pyran-4-one (1) and (2R)-2, 3- dihydro-7-hydroxy-6, 8-dimethyl-2-[(E)-prop-1-enyl] chromen-4-one (2), together with six known compounds (3-8), were isolated from a deep-sea fungus, identified as Aspergillus sydowi, by a bioassay-guided method. Their structures were elucidated by spectroscopic methods and the cytotoxicities were evaluated by SRB method.
