ABSTRACT
Prostate cancer is the most prevalent type of cancer in the United States. The most common site of prostate cancer metastasis is bone. CXCL12 is preferentially expressed in bone and is targeted by prostate cancer cells, which over-express the receptor for CXCL12, CXCR4. In response to CXCL12 stimulation, Rac1, a GTPase, along with its effectors, regulates actin polymerization to form lamellipodia, which is a critical event for cell migration. Cortactin, an actin-binding protein, is recruited to the lamellipodia and is phosphorylated at tyrosine residues. The phosphorylated cortactin is also involved in cell migration. The inhibition of Rac1 activity using a dominant negative Rac1 impairs lamellipodial protrusion as well as cortactin translocation and cortactin phosphorylation. Denbinobin, a substance extracted from Dendrobium nobile, has anticancer effects in many cancer cell lines. Whether denbinobin can inhibit prostate cancer cell migration is not clear. Here, we report that denbinobin inhibited Rac1 activity. The inhibition of Rac1 activity prevented lamellipodial formation. Cortactin phosphorylation and translocation to the lamellipodia were also impaired, and PC3 cells were unable to migrate. These results indicate that denbinobin prevents CXCL12-induced PC3 cell migration by inhibiting Rac1 activity.
Subject(s)
Anthraquinones/pharmacology , Antineoplastic Agents, Phytogenic , Cell Movement/drug effects , Dendrobium/chemistry , Phenanthrenes/pharmacology , Prostatic Neoplasms/pathology , rac1 GTP-Binding Protein/antagonists & inhibitors , Actins/metabolism , Anthraquinones/therapeutic use , Chemokine CXCL12/physiology , Cortactin/metabolism , Humans , Male , Phenanthrenes/therapeutic use , Phosphorylation , Polymerization/drug effects , Prostatic Neoplasms/metabolism , Pseudopodia/metabolism , Tumor Cells, Cultured , rac1 GTP-Binding Protein/physiologyABSTRACT
Phytochemical investigation of the roots and stems of Illigera luzonensis afforded two new aporphine alkaloids (1) and (2), one new bisdehydroaporphine alkaloid (3), and one new benzenoid (4), along with 28 known structures. The structures of new compounds were elucidated by spectral and MS analysis. Among the isolated compounds, (1) and (4-13) were subjected into the examination for their inhibitory effects on the aggregation of washed rabbit platelets.
Subject(s)
Hernandiaceae/chemistry , Plant Extracts/pharmacology , Platelet Aggregation/drug effects , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Aporphines/chemistry , Hernandiaceae/metabolism , Magnetic Resonance Spectroscopy , Molecular Conformation , Plant Extracts/chemistry , Plant Roots/chemistry , Plant Roots/metabolism , Plant Stems/chemistry , Plant Stems/metabolism , Platelet Aggregation Inhibitors/pharmacology , RabbitsABSTRACT
Two new glucosides, salviadigitoside A (1) and salviatalin A-19-O-ß-glucoside (2), belonging to the salviatalin type diterpenoids, and a new cyclopenta[c]pyridine, salviadiginine A (3), were isolated from the roots of Salvia digitaloids. Structures of these compounds were determined on the basis of spectroscopic analysis. In addition, compounds 1-3 were evaluated for their anti-inflammatory activity, but the results showed a weak anti-inflammatory activity.
Subject(s)
Anti-Inflammatory Agents/chemistry , Diterpenes/chemistry , Glucosides/chemistry , Plant Extracts/chemistry , Salvia/chemistry , Adult , Anti-Inflammatory Agents/pharmacology , Diterpenes/pharmacology , Glucosides/pharmacology , Humans , Neutrophils/drug effects , Plant Extracts/pharmacology , Plant Roots/chemistryABSTRACT
A new and efficient synthetic pathway employed the aldol condensation between the acetophenone (3) and vanillin derivative (4) resulted in the precursor chalcone intermediate (14). The target compound viscolin (1) could be afforded through the hydrogenation of the chalcone and followed by deprotection. The present strategy described the development of a more efficient procedure that allowed large-scale production of viscolin for the further research of biological activity both in vitro and in vivo.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Biphenyl Compounds/chemistry , Nitric Oxide Synthase Type II/antagonists & inhibitors , Propane/analogs & derivatives , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Biphenyl Compounds/chemical synthesis , Biphenyl Compounds/pharmacology , Cell Line, Tumor , Chalcone/chemistry , Macrophages/drug effects , Macrophages/metabolism , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Propane/chemical synthesis , Propane/chemistry , Propane/pharmacologyABSTRACT
In the present report, a concise synthesis of viscolin (1) has been achieved. The anti-inflammatory effect of viscolin was investigated in vitro and in vivo. Viscolin blocked the expression of iNOS and COX-2, and it also inhibited the ERK for the activation of NF-κB in LPS-stimulated RAW 264.7 macrophages. Western blotting and immunohistochemical analysis revealed that viscolin decreased Carr-induced iNOS and COX-2 expressions. These results could help to deduce the anti-inflammatory mechanisms.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Biphenyl Compounds/chemical synthesis , Biphenyl Compounds/pharmacology , Propane/analogs & derivatives , Animals , Anti-Inflammatory Agents/pharmacology , Blotting, Western , Cell Line , Cyclooxygenase 2/metabolism , Dinoprostone/antagonists & inhibitors , Dinoprostone/metabolism , Edema/drug therapy , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Immunohistochemistry , Macrophages/drug effects , Macrophages/metabolism , Mice , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Propane/chemical synthesis , Propane/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Three new [n-pentyl beta-carboline-1-propionate (1), 5-hydroxymethyl-9-methoxycanthin-6-one (2), and 1-hydroxy-9-methoxycanthin-6-one (3)] and 19 known beta-carboline alkaloids were isolated from the roots of Eurycoma longifolia. The new structures were determined by comprehensive analyses of their 1D and 2D NMR and mass spectral data and by chemical transformation. These compounds were screened for in vitro cytotoxic and antimalarial activities, and 9-methoxycanthin-6-one (4) and canthin-6-one (5) demonstrated significant cytotoxicity against human lung cancer (A-549) and human breast cancer (MCF-7) cell lines.
