RRC ID 39111
Author Gohda E, Okauchi H, Iwao M, Yamamoto I.
Title Induction of apoptosis by hepatocyte growth factor/scatter factor and its augmentation by phorbol esters in Meth A cells.
Journal Biochem Biophys Res Commun
Abstract Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine with mitogenic, motogenic, and morphogenic activities. In addition, HGF/SF inhibits the proliferation of some tumor cell lines, but its mechanism remains poorly understood. We determined in this study whether HGF/SF induces cell death of a Meth A mouse sarcoma cell line in vitro, whose proliferation is remarkably suppressed by HGF/SF. Inhibition of Meth A cell growth by HGF/SF was dose-dependent and maximal at a concentration of 30 ng/ml. The percentage of dead cells increased to 22% upon treatment with 30 ng/ml of HGF/SF for 96 h, whereas that in untreated cultures was less than 5%. Staining of these cells nuclei with Hoechst 33342 revealed condensation of the chromatin and nuclear fragmentation. Gel electrophoresis of DNA from HGF/SF-treated cells showed a typical ladder pattern. Cells with a fractional DNA content also increased five-fold in the HGF/SF-treated cultures as analyzed by flow cytometry after propidium iodide staining. These are features typical of apoptosis. Concurrent addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) with HGF/SF augmented the apoptosis induced by the growth factor, while TPA alone caused little death. This enhancement was largely blocked by addition of the specific protein kinase C inhibitor GF 109203X. These results indicate that HGF/SF induced the apoptotic cell death of the Meth A sarcoma cell line and that protein kinase C activation augmented the growth factor-induced apoptosis.
Volume 245(1)
Pages 278-83
Published 1998-4-7
DOI 10.1006/bbrc.1998.8416
PII S0006-291X(98)98416-9
PMID 9535822
MeSH Animals Apoptosis / drug effects* Benzimidazoles / metabolism Cell Cycle / physiology Cell Survival / drug effects DNA Fragmentation / drug effects DNA Replication / drug effects Flow Cytometry Fluorescent Dyes / metabolism Hepatocyte Growth Factor / pharmacology* Indoles / pharmacology Maleimides / pharmacology Mice Protein Kinase C / antagonists & inhibitors Tetradecanoylphorbol Acetate / pharmacology* Tumor Cells, Cultured
IF 2.985
Times Cited 33
Human and Animal Cells Meth-A(RCB0464)