The effect of nerve growth factor (NGF) on the activity and intracellular localization of protein kinase C (PKC) in pheochromocytoma PC12 cells was studied. By using immunoblotting, immunofluorescence method and phorbol ester binding, NGF was found to induce PKC translocation from the cytoplasm into the cell membrane. This process was accompanied by an increase in the protein kinase activity in the membrane fraction. Translocation was completely blocked by H-7, a protein kinase inhibitor potentiating the neurite-stimulating activity of NGF.
Using poly(lactic-co-glycolic) acid we developed a polymeric form of niclosamide (PFN) and investigated molecular mechanisms underlying its antitumor activity against human colorectal cancer cell lines (SW837, Caco-2, COLO 320 HSR). PFN was shown to be more cytotoxic against cancer cells and less cytotoxic against normal cells (human embryonic lung fibroblasts) as compared to niclosamide. Both niclosamide and its polymeric form caused mitochondrial damage (evaluated as a decrease in rhodamine 123 accumulation) and increased the levels of reactive oxygen species, particularly mitochondrial superoxide, resulting in the oxidative damage to biomolecules. Furthermore, niclosamide and PFN induced G0/G1 cell cycle arrest.
The present work relates to the field of pharmacology and medicine, in particular, to a new generation of anticancer drugs based on biocompatible polymers containing etoposide as the drug substance. A polymeric composition containing a surfactant and cryoprotective agent in addition to polymer and drug substance was designed. The optimum formulation of the polymeric composition and process conditions for its preparation were selected. The samples of etoposide polymeric forms were found to exhibit in vitro cytotoxic activity against two human tumor cell lines, viz., MCF-7 breast adenocarcinoma and K562 myeloleukemia cell lines, which was either identical or higher than the activity of free etoposide. The samples of the PLGA-based polymeric form of etoposide exhibited the highest activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.