title: Inhibition of FLT3 expression by green tea catechins in FLT3 mutated-AML cells.
abstract: Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a block in differentiation and uncontrolled proliferation. FLT3 is a commonly mutated gene found in AML patients. In clinical trials, the presence of a FLT3-ITD mutation significantly correlates with an increased risk of relapse and dismal overall survival. Therefore, activated FLT3 is a promising molecular target for AML therapies. In this study, we have shown that green tea polyphenols including (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) suppress the proliferation of AML cells. Interestingly, EGCG, EGC and ECG showed the inhibition of FLT3 expression in cell lines harboring FLT3 mutations. In the THP-1 cells harboring FLT3 wild-type, EGCG showed the suppression of cell proliferation but did not suppress the expression of FLT3 even at the concentration that suppress 100% cell proliferation. Moreover, EGCG-, EGC-and ECG-treated cells showed the suppression of MAPK, AKT and STAT5 phosphorylation. Altogether, we suggest that green tea polyphenols could serve as reagents for treatment or prevention of leukemia harboring FLT3 mutations.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Bui Thi Kim
authors.initials: BT
authors.lastname: Ly
authors.forename: Hoang Thanh
authors.initials: HT
authors.lastname: Chi
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kano
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nakano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016254:Mutagenesis, Insertional; D010766:Phosphorylation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D050799:STAT5 Transcription Factor; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine; C057580:gallocatechol; C059539:midostaurin