Down-regulation of the human VEGF gene expression by perylene monoimide derivatives.

The proximal promoter region of the human vascular endothelial growth factor (VEGF) gene contains a guanine-rich strand that can act as a transcriptional silencer by forming an intramolecular G-quadruplex. In this study, we compared two perylene monoimide derivatives, PM1 and PM2, with the well-studied perylene diimide derivative, PIPER, and the well-studied porphyrin derivative, TmPyP(4), with regard to G-quadruplex formation, G-quadruplex binding selectivity, and human VEGF gene silencing in A549 lung cancer cells. The results show that these perylene derivatives can preferentially induce intramolecular G-quadruplex formation from a duplex containing the VEGF G-quadruplex motif in vitro. Incubating A549 lung cancer cells with these perylene derivatives, especially PM2, led to the reduction of both VEGF mRNA and VEGF protein. This study might provide the foundation for the rational design and development of new perylene derivatives as effective anti-angiogenesis agents for cancer therapy.
AuthorsThanachai Taka, Khajohn Joonlasak, Liming Huang, T Randall Lee, Suk-Wah Tam Chang, Wirote Tuntiwechapikul
JournalBioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 1 Pg. 518-22 (Jan 1 2012) ISSN: 1464-3405 [Electronic] England
PMID22104143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Imides
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • perylenediimide
  • Perylene
  • Angiogenesis Inhibitors (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Design
  • G-Quadruplexes
  • Gene Expression Profiling
  • Gene Expression Regulation (drug effects)
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Imides (chemistry, pharmacology)
  • Models, Biological
  • Models, Chemical
  • Perylene (analogs & derivatives, chemistry, pharmacology)
  • Polymerase Chain Reaction (methods)
  • RNA, Messenger (metabolism)
  • Vascular Endothelial Growth Factor A (biosynthesis, metabolism)

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