ABSTRACT
Carcinoids are slow-growing neuroendocrine tumors (NETs) that are characterized by hormone overproduction; surgery is currently the only option for treatment. Activation of the Notch pathway has previously been shown to have a role in tumor suppression in NETs. The marine-derived thiodepsipeptide thiocoraline was investigated in vitro in two carcinoid cell lines (BON and H727). Carcinoid cells treated with nanomolar concentrations of thiocoraline resulted in a decrease in cell proliferation and an alteration of malignant phenotype evidenced by decrease of NET markers, achaete-scute complex like-1, chromogranin A and neurospecific enolase. Western blotting analysis demonstrated the activation of Notch1 on the protein level in BON cells. Additionally, thiocoraline activated downstream Notch targets HES1, HES5 and HEY2. Thiocoraline effectively suppressed carcinoid cell growth by promoting cell cycle arrest in BON and H727 cells. An in vivo study demonstrated that thiocoraline, formulated with polymeric micelles, slowed carcinoid tumor progression. Thus the therapeutic potential of thiocoraline, which induced activation of the Notch pathway, in carcinoid tumors was demonstrated.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoid Tumor/metabolism , Carcinoid Tumor/pathology , Depsipeptides/pharmacology , Receptors, Notch/metabolism , Signal Transduction/drug effects , Animals , Antineoplastic Agents/administration & dosage , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoid Tumor/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Depsipeptides/administration & dosage , Disease Models, Animal , Disease Progression , Dose-Response Relationship, Drug , Humans , Male , Tumor Burden/drug effects , Xenograft Model Antitumor AssaysABSTRACT
An integrated and coordinated set of programs has been established to meet ICBG goals in Papua New Guinea (PNG). Here we give an overview of the PNG ICBG and focus on the key elements and major steps taken to establish a program necessary for the pharmacological assessment of botanicals and traditional medicines in PNG and, by extrapolation, in other developing countries.
ABSTRACT
Aspergillus parasiticus, a fungal isolate from a coast redwood tree (Sequoia sempervirens), has been shown to produce four new compounds, sequoiatones C-F (1-4). The structures of these compounds, all of which are cytotoxic to brine shrimp, were deduced by spectral analysis.
Subject(s)
Aspergillus/chemistry , Cycadopsida/chemistry , Heterocyclic Compounds, 2-Ring/isolation & purification , Animals , Artemia/drug effects , California , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Structure-Activity Relationship , Toxicity TestsSubject(s)
Anti-Bacterial Agents/chemistry , Aspergillus niger/chemistry , Cyclohexanes/chemistry , Epoxy Compounds/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , StereoisomerismABSTRACT
A novel lactone, gloeolactone (1), has been isolated from the blue-green alga, Gloeotrichia sp. The structure of this compound has been elucidated from a detailed analysis of the NMR spectra. This compound was shown to be toxic to brine shrimp.
