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Nitrosamine-induced lung carcinogenesis and Ca2+/calmodulin antagonists
1Department of Pathobiology, University of Tennessee, Knoxville 37901.
Cancer Research
|May 1, 1992
Summary
Tobacco carcinogens like nitrosamines activate nicotinic receptors, promoting lung cancer cell growth. A novel compound, B859-35, shows promise in inhibiting neuroendocrine lung tumor proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cell membrane receptors and signal transduction pathways are implicated in tobacco-related lung carcinogenesis.
- Nicotine and tobacco-specific nitrosamines are potential molecular targets for lung cancer therapy.
Purpose of the Study:
- To review recent data on molecular targets in tobacco-related lung carcinogenesis.
- To explore the therapeutic potential of novel compounds against neuroendocrine lung tumors.
Main Methods:
- Review of existing literature on nitrosamine binding to nicotinic cholinergic receptors.
- In vitro and in vivo studies on the antiproliferative effects of dihydropyridine derivative B859-35 on lung tumor cells.
- Investigation of B859-35's mechanism of action, including inhibition of Ca2+/calmodulin and protein kinase C.
Main Results:
- N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bind to nicotinic cholinergic receptors in hamster lung.
- Nitrosamine and nicotine binding stimulates proliferation of human lung carcinoid cells in vitro.
- B859-35 exhibits selective antiproliferative effects on neuroendocrine lung tumor cells.
Conclusions:
- Chronic stimulation of nicotinic receptors by nicotine and nitrosamines may drive neuroendocrine lung tumor development in smokers.
- B859-35's inhibition of key signal transduction pathways suggests its potential as a therapeutic agent for neuroendocrine lung cancers.