A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.
Acute myeloid leukemia (AML) is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA) has been successfully introduced to treat acute promyelocytic leukemia (APL), it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA) were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA). Furazolidone (FZD) was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.
Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan, Hubei, China.
Xueqing
X
Jiang
Lin
L
Sun
Jihui Julia
JJ
Qiu
Xiujing
X
Sun
Sen
S
Li
Xiyin
X
Wang
Chi Wai Eric
CW
So
Shuo
S
Dong
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000994:Antitrichomonal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D058492:Drug Repositioning; D005664:Furazolidone / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D000994:Antitrichomonal Agents; D015514:Oncogene Proteins, Fusion; D016159:Tumor Suppressor Protein p53; D005664:Furazolidone