PMID: 11315101Apr 21, 2001Paper

Inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, suppresses invasion ability by reducing productions of matrix metalloproteinase-2 and -9 and cell motility in HSC-4 tongue carcinoma cell line

Clinical & Experimental Metastasis
Y BabaY Kato

Abstract

Inostamycin is an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase. It significantly reduced epidermal growth factor (EGF)-induced in vitro invasion of the tongue carcinoma cell line, HSC-4, through reconstituted basement membrane Matrigel. Since phosphatidylinositol (PI) 4,5-biphosphate is important for signal transduction through protein kinase C and actin reorganisation, we further examined the effect of inostamycin on production of two matrix metalloproteinases (MMPs), MMP-2 and -9, and on cell motility. Zymographic analysis showed that inostamycin suppressed pro-MMP-2 and pro-MMP-9 levels at a dose-dependent fashion, while MMP-2 activity was not significantly affected. By reverse transcription-polymerase chain reaction, it was found that inostamycin diminished steady state levels of MMP-2 and -9 but not membrane type 1-MMP mRNA expressions. Inostamycin partially blocked both EGF- and phorbol 12-myristate 13-acetate-stimulated pro-MMP-9 production. A cytoplasmic calcium chelator (BAPTA-AM) dramatically elevated pro- MMP-9 and slightly elevated pro-MMP-2 secretions. EGF-stimulated motility of HSC-4 cells was suppressed by inostamycin treatment along with reduction of actin cytoskelet...Continue Reading

Citations

Nov 1, 2003·Cancer Chemotherapy and Pharmacology·Xian-Ming ZhangQiang Xu
Dec 7, 2005·International Journal of Cancer. Journal International Du Cancer·Pia HeikkiläTuula Salo
Dec 11, 2014·Cancer Cell International·Atsuko SuzukiYasumasa Kato
May 1, 2012·Journal of Oncology·Yuh BabaYasumasa Kato
Sep 14, 2001·Biochemical and Biophysical Research Communications·Y KatoR I Hata

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