Molecular mechanism of the inhibitory effect of KS-5 on bFGF-induced angiogenesis in vitro and in vivo

Chieh Yu Peng, Shiow Lin Pan, Kuo Hsiung Lee, Kenneth F. Bastow, Che Ming Teng

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Inhibition of angiogenesis controls the expansion and metastasis of many solid tumors and other related-diseases. KS-5 (1,7-dihydroxy-3-methoxyacridone), is an inactive analogue of the substituted 1-hydroxy acridone antiviral class. This study aimed at studying the effects of KS-5 on bFGF-induced angiogenesis in cultured human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. KS-5 inhibited bFGF (10 ng/ml)-induced cell proliferation in a concentration-dependent manner, but did not exhibit significant cytotoxic effect examined by LDH release assay. KS-5 inhibited bFGF-induced angiogenesis was associated with decreasing DNA synthesis as evaluated by BrdU incorporation assay, and abrogating endothelial cell ERK1/2 and Akt protein phosphorylation, the major signaling pathways involved in cellular processes of angiogenesis. In addition, KS-5 also inhibited bFGF-induced phosphorylation of mTOR and the major downstream effectors, eIF4E and p70S6K. Moreover, bFGF-induced protein synthesis was also inhibited by KS-5. Most importantly, KS-5 treatment in nude mice inhibited in vivo angiogenesis as revealed by Matrigel implant assay. In conclusion, the present study suggests that KS-5 has potential anti-angiogenetic effect for cancer therapy and other angiogenesis-dependent diseases.

Original languageEnglish
Pages (from-to)114-121
Number of pages8
JournalCancer Letters
Volume263
Issue number1
DOIs
Publication statusPublished - May 8 2008
Externally publishedYes

Fingerprint

Phosphorylation
70-kDa Ribosomal Protein S6 Kinases
Human Umbilical Vein Endothelial Cells
Bromodeoxyuridine
Nude Mice
Antiviral Agents
Neoplasms
Proteins
Endothelial Cells
Cell Proliferation
Neoplasm Metastasis
DNA
In Vitro Techniques
Therapeutics
acridone
matrigel
1,7-dihydroxy-3-methoxyacridone

Keywords

  • Acridone derivatives
  • Angiogenesis
  • Endothelial cells

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Molecular mechanism of the inhibitory effect of KS-5 on bFGF-induced angiogenesis in vitro and in vivo. / Peng, Chieh Yu; Pan, Shiow Lin; Lee, Kuo Hsiung; Bastow, Kenneth F.; Teng, Che Ming.

In: Cancer Letters, Vol. 263, No. 1, 08.05.2008, p. 114-121.

Research output: Contribution to journalArticle

Peng, Chieh Yu ; Pan, Shiow Lin ; Lee, Kuo Hsiung ; Bastow, Kenneth F. ; Teng, Che Ming. / Molecular mechanism of the inhibitory effect of KS-5 on bFGF-induced angiogenesis in vitro and in vivo. In: Cancer Letters. 2008 ; Vol. 263, No. 1. pp. 114-121.
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