Induction of apoptosis by hepatocyte growth factor/scatter factor and its augmentation by phorbol esters in Meth A cells

Biochemical and Biophysical Research Communications
E GohdaI Yamamoto

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 enhan...Continue Reading

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Citations

Oct 6, 2007·Cell Death and Differentiation·D Tulasne, B Foveau
Mar 9, 2005·ORL; Journal for Oto-rhino-laryngology and Its Related Specialties·Ramin NaimKarl Hormann
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