G-quadruplex compounds and cis-platin act synergistically to inhibit cancer cell growth in vitro and in vivo

Gunaratnam, M., Green, C., Moreira, J. B., Moorhouse, A. D., Kelland, L. R., Moses, J. E., Neidle, S. (July 2009) G-quadruplex compounds and cis-platin act synergistically to inhibit cancer cell growth in vitro and in vivo. Biochem Pharmacol, 78 (2). pp. 115-22. ISSN 0006-2952

URL: https://pubmed.ncbi.nlm.nih.gov/19475728/
DOI: 10.1016/j.bcp.2009.03.018


The ability of two structurally diverse telomeric G-quadruplex-binding compounds to synergise the action of cis-platin has been investigated in two cancer cell lines. One compound is a trisubstituted acridine compound AS1410, a close analogue of BRACO-19, and the other is a non-polycyclic compound synthesised using click chemistry and containing two triazole rings. Both compounds produce growth arrest at sub-cytotoxic concentrations in the two cell lines (MCF7 and A549), with behaviour consistent with telomere targeting mechanisms. Synergistic behaviour was observed in both cell lines with both compounds in combination with cis-platin, but only when the ratio of AS1410:cis-platin is >1. In vivo tumour xenograft studies with the A549 lung cancer model and the trisubstituted acridine compound AS1410 showed only a modest anti-tumour effect when administered alone, but produced rapid and highly significant decreases in tumour volume when administered in combination with cis-platin.

Item Type: Paper
Additional Information: Biochemical pharmacology
Uncontrolled Keywords: Animals Antineoplastic Agents/*administration & dosage/pharmacology Antineoplastic Combined Chemotherapy Protocols/administration & dosage/pharmacology Cell Line Cell Line, Tumor Cisplatin/*administration & dosage/pharmacology Drug Synergism Female *G-Quadruplexes Growth Inhibitors/*administration & dosage/pharmacology Humans Mice Mice, Nude Neoplasms/*drug therapy/*pathology Time Factors Xenograft Model Antitumor Assays/methods
CSHL Authors:
Communities: CSHL labs > Moses lab
Depositing User: Matthew Dunn
Date: 15 July 2009
Date Deposited: 19 Apr 2021 20:08
Last Modified: 19 Apr 2021 20:08
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39536

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving