Diacylglycerol (DAG)-lactones, a New Class of Protein Kinase C (PKC) Agonists, Induce Apoptosis in LNCaP Prostate Cancer Cells
نویسندگان
چکیده
From the ‡Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, the ¶Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, the Department of Microbiology, School of Pharmaceutical Sciences, Showa University, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan, the **Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlin-Dong, Kwanak-ku, Seoul 151-742, South Korea, and the ‡‡Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21701
منابع مشابه
Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCalpha.
Phorbol esters, the archetypical (PKC) activators, induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. In this study we evaluate the effect of a novel class of PKC ligands, the diacylglycerol (DAG)-lactones, as inducers of apoptosis in LNCaP cells. These unique ligands were designed using novel pharmacophore- and receptor-guided approaches to achieve highly potent DAG surrogates...
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Diacylglycerol lactones built with a rigid 4-[(methylphenyl)ethynyl]phenyl rod that is separated from the exocyclic acylcarbonyl of the DAG-lactone core by a spacer unit of variable length were synthesized and studied. Binding affinities for a panel of classical and novel PKC isozymes in two different phospholipid environments, one corresponding to the plasma membrane of cells, were determined....
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