Inostamycin prevents malignant phenotype of cancer: Inhibition of phosphatidylinositol synthesis provides a therapeutic advantage for head and neck squamous cell carcinoma

Yuh Baba, Yasumasa Kato, Kaoru Ogawa

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8 Citations (Scopus)

Abstract

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'.

Original languageEnglish
Pages (from-to)171-175
Number of pages5
JournalCell Biology International
Volume34
Issue number2
DOIs
Publication statusPublished - 2010 Feb

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Phosphatidylinositols
Cyclin D1
Head and Neck Neoplasms
Matrix Metalloproteinases
Phenotype
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
G1 Phase Cell Cycle Checkpoints
Neoplasms
Matrix Metalloproteinase 2
Extracellular Signal-Regulated MAP Kinases
Streptomyces
Treatment Failure
Vascular Endothelial Growth Factor A
Cell Movement
Therapeutics
Endothelial Cells
Anti-Bacterial Agents
Cell Line
Growth
inostamycin

Keywords

  • Cyclin D1
  • Head and neck cancer
  • Inostamycin
  • Matrix metalloproteinase (MMP)-2 and -9
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Cell Biology

Cite this

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