title: Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways.
abstract: Icaritin, a hydrolytic product of icaritin, is isolated from the traditional Chinese medicinal herb epimedium. Icaritin inhibits the proliferation of several tumor cell lines, but its effect on acute myeloid leukemia (AML) and underlying mechanisms remain to be identified. In the present study, we demonstrated that icaritin inhibits the proliferation of human AML cell lines NB4, HL60, and U937, in a dose- and time-dependent manner. Importantly, icaritin showed anti-leukemia activity on bone marrow mononuclear cells from 15 newly diagnosed AML patients. Flow cytometry analyses indicated that icaritin induces AML cells apoptosis. Icaritin induced activation of caspase-9, -3, -7 and the cleavage of PARP as measured by Western blotting. Icaritin downregulates p-ERK and p-AKT and inhibits the expression of c-myc. These results suggest that icaritin is a promising candidate drug for the treatment of AML. The underlying mechanisms of icaritin anti-AML activity are associated with inhibition of the MAPK/ERK and PI3K/AKT signals and downregulation of c-myc.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, People's Republic of China.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Huai
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.forename: Cuicui
authors.initials: C
authors.lastname: Wang
authors.forename: Yujjao
authors.initials: Y
authors.lastname: Jia
authors.forename: Yirui
authors.initials: Y
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Houcai
authors.initials: H
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Rao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells; D055815:Young Adult
chemical_list: D005419:Flavonoids; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; C499403:icaritin
references.citation: Mol Cancer Ther. 2012 May;11(5):1155-65
references.pmid: 22389469
references.citation: Leuk Res. 2007 Apr;31(4):523-30
references.pmid: 17007926
references.citation: Haematologica. 2007 Jan;92(1):81-94
references.pmid: 17229639
references.citation: Mol Biol Cell. 2002 Aug;13(8):2598-606
references.pmid: 12181332
references.citation: Neuroscience. 2007 Mar 30;145(3):911-22
references.pmid: 17321691
references.citation: Planta Med. 2010 Nov;76(16):1834-9
references.pmid: 20560114
references.citation: PLoS One. 2011;6(8):e23720
references.pmid: 21887305
references.citation: Eur J Pharmacol. 2004 Nov 19;504(3):147-53
references.pmid: 15541416
references.citation: Eur J Pharmacol. 2011 May 11;658(2-3):114-22
references.pmid: 21376032
references.citation: Acta Pharmacol Sin. 2005 Apr;26(4):477-85
references.pmid: 15780198
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4826-31
references.pmid: 18344322
references.citation: Blood. 2007 Apr 15;109(8):3441-50
references.pmid: 17197433
references.citation: Oncogene. 2008 Oct 27;27(50):6462-72
references.pmid: 18955973
references.citation: Expert Opin Investig Drugs. 2011 Oct;20(10):1377-95
references.pmid: 21895538
references.citation: Hematology Am Soc Hematol Educ Program. 2004;:98-117
references.pmid: 15561679
references.citation: Biochem Biophys Res Commun. 2002 Aug 30;296(4):942-8
references.pmid: 12200139
references.citation: PLoS One. 2011 Mar 08;6(3):e16781
references.pmid: 21408143
references.citation: Eur J Pharmacol. 2011 Sep 30;667(1-3):129-35
references.pmid: 21699893