Novel activity of acriflavine against colorectal cancer tumor cells
Open Access
- 12 September 2011
- journal article
- Published by Wiley in Cancer Science
- Vol. 102 (12), 2206-2213
- https://doi.org/10.1111/j.1349-7006.2011.02097.x
Abstract
A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs. (Cancer Sci 2011; 102: 2206–2213)Keywords
This publication has 34 references indexed in Scilit:
- Anti-cancer natural products isolated from chinese medicinal herbsChinese Medicine, 2011
- Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularizationProceedings of the National Academy of Sciences of the United States of America, 2009
- Identification of a Novel Topoisomerase Inhibitor Effective in Cells Overexpressing Drug Efflux TransportersPLOS ONE, 2009
- Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved ChemotherapyJournal of Clinical Oncology, 2009
- Pharmacological profiling of novel non-COX-inhibiting indole-pyran analogues of etodolac reveals high solid tumour activity of SDX-308 in vitroInvestigational New Drugs, 2007
- Screening of an annotated compound library for drug activity in a resistant myeloma cell lineCancer Chemotherapy and Pharmacology, 2006
- Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profilesBritish Journal of Cancer, 2005
- Inhibition of lipopolysaccharide-induced I-κB degradation and tumor necrosis factor-α expression by acriflavine, an antimicrobial agentInternational Journal of Immunopharmacology, 2000
- From amsacrine to DACA (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide): Selectivity for topoisomerases I and II among acridine derivativesEuropean Journal of Cancer, 1996
- Detection of tumor‐specific cytotoxic drug activity IN VITRO using the fluorometric microculture cytotoxicity assay and primary cultures of tumor cells from patientsInternational Journal of Cancer, 1994