Novel activity of acriflavine against colorectal cancer tumor cells

被引：59

作者：

Hassan, Saadia ^{[1
]}

Laryea, Daniel ^{[1
]}

Mahteme, Haile ^{[2
]}

Felth, Jenny ^{[3
]}

Fryknas, Marten ^{[1
]}

Fayad, Walid ^{[4
]}

Linder, Stig ^{[4
]}

Rickardson, Linda ^{[1
]}

Gullbo, Joachim ^{[1
]}

Graf, Wilhelm ^{[2
]}

Pahlman, Lars ^{[2
]}

Glimelius, Bengt ^{[4
,5
]}

Larsson, Rolf ^{[1
]}

Nygren, Peter ^{[5
]}

机构：

[1] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[2] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden

[3] Uppsala Univ, Dept Med Chem, Uppsala, Sweden

[4] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden

[5] Uppsala Univ, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden

来源：

CANCER SCIENCE | 2011年 / 102卷 / 12期

关键词：

MICROCULTURE CYTOTOXICITY ASSAY; POTENTIAL ANTITUMOR AGENT; DRUG ACTIVITY; IN-VITRO; PRIMARY CULTURES; ACRIDINE; IDENTIFICATION; EXPRESSION; GUANOSINE; GROWTH;

D O I：

10.1111/j.1349-7006.2011.02097.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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: 22062213)

引用

页码：2206 / 2213

页数：8

共 36 条

[1] EXPERIMENTAL SOLID TUMOR-ACTIVITY OF N-[2-(DIMETHYLAMINO)ETHYL]-ACRIDINE-4-CARBOXAMIDE [J].