ABSTRACT
Universal phenotyping techniques that can discriminate among various states of biological systems have great potential. We applied 557 fluorescent library compounds to NCI's 60 human cancer cell-lines (NCI-60) to generate a systematic fluorescence phenotypic profiling data. By the kinetic fluorescence intensity analysis, we successfully discriminated the organ origin of all the 60 cell-lines.
Subject(s)
Gene Expression Regulation, Neoplastic , Boron Compounds/pharmacology , Cell Line, Tumor , Cluster Analysis , Fluorescence , Fluorescent Dyes/chemistry , Gene Expression Profiling , Humans , Kinetics , Microscopy, Fluorescence/methods , Organic Chemicals/pharmacology , PhenotypeABSTRACT
During muscle differentiation, mitochondria undergo dramatic changes in their morphology and distribution to prepare for the higher rate of energy consumption. By applying a mitochondria-targeted rosamine library in C2C12 myogenesis, we discovered one compound that controls muscle differentiation. When treated to undifferentiated myoblasts, our selected compound, B25, inhibited myotube formation, and when treated to fully differentiated myotubes, it induced fission of multinucleated myotubes into mononucleated fragments. Compared to myoseverin, which is known for inducing myotube fission by destabilizing microtubules, B25 affects neither microtubule stability nor cell cycle. Further investigation identified that B25 induces myotube fission through the activation of NF-kappaB, which is one of the important signaling pathways linked to skeletal muscle differentiation. So far, the use of small-molecule fluorophores is limited in the discovery of labeling agents or sensors. In addition to their potential as a sensor, here we show the application of fluorescent small molecules in the discovery of a bioactive probe that induces a specific cellular response.
Subject(s)
Cell Differentiation/drug effects , Fluorescent Dyes/metabolism , Fluorescent Dyes/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/drug effects , Animals , Cells, Cultured , Mice , Molecular Weight , Muscle Fibers, Skeletal/metabolism , PC12 Cells , Purines/pharmacology , RatsABSTRACT
The main aim of this study is to determine the causes and the epidemiological aspects of sudden natural deaths. Data were collected from 545 sudden natural autopsies in UMMC, Kuala Lumpur over a five-year period, from 1st January 2000 to 31st December 2004. There were 475 males and 70 females. The largest number of sudden natural deaths was in the age group of 41-50 years. 35.8%, 30.5% and 11.7% of the patients were Chinese, Indian and Malay, respectively. A majority of the patients were married (59.8%) and came from the semiskilled-unskilled group (30.6%). The monthly distribution was almost constant. Cardiovascular diseases were the most important cause contributing 64.9% in sudden natural deaths.
