title: Novel activity of acriflavine against colorectal cancer tumor cells.
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.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden. sadia.hassan@medsci.uu.se
authors.forename: Saadia
authors.initials: S
authors.lastname: Hassan
authors.forename: Daniel
authors.initials: D
authors.lastname: Laryea
authors.forename: Haile
authors.initials: H
authors.lastname: Mahteme
authors.forename: Jenny
authors.initials: J
authors.lastname: Felth
authors.forename: Mårten
authors.initials: M
authors.lastname: Fryknäs
authors.forename: Walid
authors.initials: W
authors.lastname: Fayad
authors.forename: Stig
authors.initials: S
authors.lastname: Linder
authors.forename: Linda
authors.initials: L
authors.lastname: Rickardson
authors.forename: Joachim
authors.initials: J
authors.lastname: Gullbo
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Graf
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Peter
authors.initials: P
authors.lastname: Nygren
mesh_terms: D000167:Acriflavine / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D000077146:Irinotecan; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008297:Male; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D000077150:Oxaliplatin; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D000077150:Oxaliplatin; D000167:Acriflavine; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D005472:Fluorouracil; D002166:Camptothecin