Subject(s)
Humans , Male , Benzodiazepines , Heterocyclic Compounds , Heterocyclic Compounds, 2-RingABSTRACT
1KE8 is known as a potential target for anti-cancer medication. Indoles are biologically active nitrogen heterocyclics known for broad spectrum activities. Modification of Indole ring system with selected structural descriptors has offered a high degree of stereo specificity and diversity in activity to the moiety.
Subject(s)
Antineoplastic Agents/pharmacokinetics , Binding Sites , Computer Simulation , Cyclin-Dependent Kinase 8/metabolism , Heterocyclic Compounds, 2-Ring/pharmacokinetics , Indoles/classification , Indoles/pharmacokinetics , Molecular Docking Simulation , Molecular Dynamics SimulationABSTRACT
Herb combination has been very popular in traditional medical prescriptions such as Traditional Chinese Medicine [TCM]. Persistent efforts and attempts have been made to dissect the action mode of TCM in recent years, which has provided certain evidence for inter-herbal interactions. However, the interactions among different components in a single herb have been largely neglected. In this experimental study, the interactions among different components of a single herb were explored. The effect of three main sesquiterpenes [germacrone, curdione, furanodiene] isolated from Curcuma WenyujinY.H. Chenet C Ling on MDA-MB-231 and MCF-7 breast cancer cell proliferation alone or in combination with a fixed-dose-combination was investigated. Furanodiene significantly inhibited cancer cell proliferation while germacrone and curdione showed no effect. Germacrone enhanced furanodiene's anti-proliferative effect. Curdione showed no effect on furanodiene's anti-proliferative effect but partly reversed the anti-proliferative effect of germacrone and furanodiene combined. The morphological and mitochondrial membrane potential [delta [PSI]m] changes showed similar results. However, they demonstrated complicated interactions on the expression of apoptotic-related proteins and key signal transduction proteins. Unpredictable and complex interactions among different components in Curcuma WenyujinY.H.Chenet C Ling may exist. The intra-herb interactions should be taken into consideration when attempts are made to interpret the art of TCM formulation or other similar recipes
Subject(s)
Humans , Sesquiterpenes, Germacrane , Furans , Heterocyclic Compounds, 2-Ring , Cell Proliferation , Herb-Drug Interactions , Medicine, Chinese TraditionalABSTRACT
The present study is to establish Caco-2/HT29-MTX co-cultured cells and investigate the transport capability of PLGA nanoparticles with different surface chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA-NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) as carrier material with surface modified by methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used as a fluorescent marker in the transport of nanoparticles investigated by confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded nanoparticles was quantitively determined by high performance liquid chromatography. Colchicine and nocodazole were used in the transport study to explore the involved endocytosis mechanisms of nanoparticles. Distribution of the tight junction proteins ZO-1 was also analyzed by immunofluorescence staining. The results showed that the nanoparticles dispersed uniformly. The zeta potential of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA-NPs was positive. The entrapment efficiency of FDE in all nanoparticles was higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine and nocodazole could significantly decrease the transport amount of nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1 protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles, which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result, mPEG-PLGA-NPs could penetrate the mucus layer rapidly and transport across Caco-2/HT29-MTX co-cultured cells.
Subject(s)
Humans , Biological Transport , Caco-2 Cells , Chitosan , Chemistry , Coated Materials, Biocompatible , Chemistry , Coculture Techniques , Drug Carriers , Furans , Chemistry , Metabolism , HT29 Cells , Heterocyclic Compounds, 2-Ring , Chemistry , Metabolism , Lactic Acid , Chemistry , Nanoparticles , Particle Size , Polyethylene Glycols , Chemistry , Polyglycolic Acid , Chemistry , Zonula Occludens-1 Protein , MetabolismABSTRACT
Heat shock protein 90 is a new target of antitumor drug, the inhibitor of Hsp90 fight against tumor by destroy and degrade the structure of protein. In recent years, looking for Hsp90 inhibitor is not only via structure modifying of natural products, but also via high throughput screening and computer aided drug design to find and synthesize new kinds of Hsp90 inhibitor. Anyway, Hsp90 inhibitor has considered as an important biology target and to pay more and more attention. This review describes recent developments of small molecule Hsp90 inhibitors.