Inhibition of protein-kinase-C--dependent cell proliferation of human lung cancer cell lines by the dihydropyridine dexniguldipine.

Abstract

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.

• Authors: H M Schuller, M Orloff, G K Reznik
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 120 Issue 6 Pg. 354-8 ( 1994) ISSN: 0171-5216 [Print] Germany
• PMID: 8138560 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Dihydropyridines
• Protein Kinase C
• niguldipine

Topics

• Adenocarcinoma (drug therapy)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Carcinoid Tumor (drug therapy)
• Carcinoma, Adenosquamous (drug therapy)
• Carcinoma, Small Cell (drug therapy)
• Carcinoma, Squamous Cell (drug therapy)
• Cell Division (drug effects)
• Dihydropyridines (pharmacology, therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, enzymology, pathology)
• Protein Kinase C (antagonists & inhibitors)
• Tumor Cells, Cultured