title: Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia.
abstract: Bioactive components from dietary supplements such as curcumin may represent attractive agents for cancer prevention or treatment. DNA methylation plays a critical role in acute myeloid leukemia (AML) development, and presents an excellent target for treatment of this disease. However, it remains largely unknown how curcumin, a component of the popular Indian spice turmeric, plays a role in DNA hypomethylation to reactivate silenced tumor suppressor genes and to present a potential treatment option for AML. Here we show that curcumin down-regulates DNMT1 expression in AML cell lines, both in vitro and in vivo, and in primary AML cells ex vivo. Mechanistically, curcumin reduced the expression of positive regulators of DNMT1, p65 and Sp1, which correlated with a reduction in binding of these transcription factors to the DNMT1 promoter in AML cell lines. This curcumin-mediated down-regulation of DNMT1 expression was concomitant with p15(INK4B) tumor suppressor gene reactivation, hypomethylation of the p15(INK4B) promoter, G1 cell cycle arrest, and induction of tumor cell apoptosis in vitro. In mice implanted with the human AML MV4-11 cell line, administration of curcumin resulted in remarkable suppression of AML tumor growth. Collectively, our data indicate that curcumin shows promise as a potential treatment for AML, and our findings provide a basis for future studies to test the clinical efficacy of curcumin - whether used as a single agent or as an adjuvant - for AML treatment.
authors: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America. Jianhua.yu@osumc.edu
authors: Jianhua
authors: J
authors: Yu
authors: Yong
authors: Y
authors: Peng
authors: Lai-Chu
authors: LC
authors: Wu
authors: Zhiliang
authors: Z
authors: Xie
authors: Youcai
authors: Y
authors: Deng
authors: Tiffany
authors: T
authors: Hughes
authors: Shun
authors: S
authors: He
authors: XiaoKui
authors: X
authors: Mo
authors: Ming
authors: M
authors: Chiu
authors: Qi-En
authors: QE
authors: Wang
authors: Xiaoming
authors: X
authors: He
authors: Shujun
authors: S
authors: Liu
authors: Michael R
authors: MR
authors: Grever
authors: Kenneth K
authors: KK
authors: Chan
authors: Zhongfa
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016329:Sp1 Transcription Factor; D051996:Transcription Factor RelA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D020169:Caspases; D003474:Curcumin