Title:Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules
Volume: 24
Issue: 42
关键词:
抗癌,致癌基因,转录调控,四联体,DNA,吲哚喹啉,卟啉,药物靶点。
摘要: Nucleic acids are prone to structural polymorphism and a number of structures
may be formed in addition to the well-known DNA double helix. Among these is a family of
nucleic acid four-stranded structures known as G-quadruplexes (G4). These quadruplex
structures can be formed by sequences containing repetitive guanine-rich tracks and the
analysis of Non-B-DNA database indicated an enrichment of these sequences in genomic
regions controlling cellular proliferation, such as for example in the promoter regions of c-
MYC, k-RAS, c-KIT, HSP90 and VEGF among others. The broad concept of G4 targeting
with small molecules is now generally accepted as a promising novel approach to anticancer
therapy and several small molecules with antiproliferative activity in cancer cell lines have
also been shown to stabilize these DNA structures, thus suggesting a potential application of
G4-interactive small molecules as new anticancer drugs. Herein we review, by targeted oncogene
and main chemical scaffold, those G4-interactive small molecules with reported gene
expression modulatory activity in cancer cell lines. The data obtained so far are encouraging
but further efforts are needed to validate G4 as drug targets and optimize the structure of G4-
interactive small molecules into new anticancer drugs.