Brought to you by Portland Press Ltd.
Published on behalf of the International Federation for Cell Biology
Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2010) 34, 171–175 (Printed in Great Britain)
Review article
Inostamycin prevents malignant phenotype of cancer: inhibition of phosphatidylinositol synthesis provides a therapeutic advantage for head and neck squamous cell carcinoma
Yuh Baba*†‡1, Yasumasa Kato‡1 and Kaoru Ogawa†
*Department of Otolaryngology, Tochigi National Hospital, Tochigi 320-8580, Japan, †Department of Otolaryngology, Head and Neck Surgery, Keio University, Tokyo 160-0082, Japan, and ‡Department of Biochemistry and Molecular Biology, Kanagawa Dental College, Yokosuka 238-8580, Japan

Head and neck squamous cell carcinoma is the sixth most common type of neoplasm worldwide, but its prognosis has not improved significantly in recent years. Therefore, efforts need to be intensified to gain a better understanding of this disease and develop novel treatment strategies. Inhibition of cytidine 5′-diphosphate 1,2-diacyl-sn-glycerol: inositol transferase by inostamycin, an antibiotic isolated from Streptomyces sp. MH816-AF15, induces G1 cell cycle arrest accompanied by a decrease in cyclin D1 and phosphorylated RB protein levels, along with suppression of in vitro invasive ability through reduced production of matrix metalloproteinases (MMP-2 and MMP-9) and cell motility in head and neck cancer cell lines. Furthermore, inostamycin abrogated the stimulatory effect of VEGF (vascular endothelial growth factor) on growth and migration activities of endothelial cells by targeting extracellular signal-regulated kinase-cyclin D1 and p38 pathways, respectively. Because inostamycin has both antiproliferative and anti-invasive abilities, inhibition of phosphatidylinositol synthesis could be a potent therapeutic strategy for head and neck cancer as the ‘cancer dormant therapy’, i.e. a therapeutic concept to prolong ‘time to treatment failure’ or ‘time to progression’.

Key words: cyclin D1, head and neck cancer, inostamycin, matrix metalloproteinase (MMP)-2 and -9, vascular endothelial growth factor (VEGF)

Abbreviations: CKI, CDK inhibitor, CDK, cyclin-dependent kinase, BM, basement membrane, HNSCC, head and neck squamous cell carcinoma, EC, endothelial cell, ERK, extracellular signal-regulated kinase, MMPs, matrix metalloproteinases, MAPK, mitogen-activated kinase, NF-κB, nuclear factor-κB, PI, phosphatidylinositol, pRB, Rb protein, VEGF, vascular endothelial growth factor

1Correspondence may be addressed to either of these authors ( or

Received 23 October 2009; accepted 13 November 2009

Published online 14 January 2010, doi:10.1042/CBI20090310

© 2010 The Author(s) Journal compilation. © 2010 Portland Press Ltd

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)