Inhibition of protein-kinase-C--dependent cell proliferation of human lung cancer cell lines by the dihydropyridine dexniguldipine.
The dihydropyridine, dexniguldipine hydrochloride (B859-35), has shown therapeutic activity in experimentally induced neuroendocrine hamster lung tumors and demonstrated antiproliferative effects in a mammary cancer cell line via inhibition of Ca2+ calmodulin. Studies in NIH 3T3 fibroblasts have provided evidence that dexniguldipine may also inhibit protein kinase C (PKC). In this study, we have tested the hypothesis that dexniguldipine may inhibit the proliferation of lung cancer cells in response to autocrine or exogenous activation of PKC. Using a panel of human lung cancer cell lines, we show that dexniguldipine is a potent inhibitor of mitogenic signal transduction pathways dependent on PKC activation in several small-cell and non-small-cell lung cancer cell lines while it failed to inhibit cyclic-AMP-dependent cell proliferation.
Schuller
H M
HM
Carcinogenesis and Developmental Therapeutics Program, College of Veterinary Medicine, University of Tennessee, Knoxville.
Orloff
M
M
Reznik
G K
GK
D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002276:Carcinoid Tumor / Q000188:drug therapy; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004095:Dihydropyridines; D011493:Protein Kinase C; C054074:niguldipine