Novel activity of acriflavine against colorectal cancer tumor cells.

Cancer science (2011-09-14)
Saadia Hassan, Daniel Laryea, Haile Mahteme, Jenny Felth, Mårten Fryknäs, Walid Fayad, Stig Linder, Linda Rickardson, Joachim Gullbo, Wilhelm Graf, Lars Påhlman, Bengt Glimelius, Rolf Larsson, Peter Nygren
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acriflavine hydrochloride
Sigma-Aldrich
Acriflavine
Sigma-Aldrich
Acriflavine, BioReagent, suitable for fluorescence, ≥90% (AT)