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Anti-cancer Effects of Curcumin on Myelodysplastic Syndrome through the Inhibition of Enhancer of Zeste Homolog-2 (EZH2)

[ Vol. 19 , Issue. ]

Author(s):

Ling Ma, Xia Zhang, Zhiqiong Wang, Lifang Huang, Fankai Meng, Lihua Hu, Yan Chen and Jia Wei*Pages 1-13 (13)

Abstract:


Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase that regulates histone H3 methylation of lysine27 (H3K27me3), is involved in the pathogenesis of myelodysplastic syndrome (MDS). Targeting epigenetic regulators has been identified as a potential treatment target in MDS chemotherapy. Curcumin, a natural compound extracted from turmeric, was found to possess a wide range of anticancer activities in various tumors. This study was designed to investigate the inhibitory effect and action mechanism of curcumin in myelodysplastic syndrome (MDS) in vitro and in vivo. Our results showed that curcumin can significantly suppress cell proliferation and induce cell apoptosis and cell cycle arrest in human MDS-derived cell lines. It reduced EZH2, DNA methyltransferase 3A (DNMT3a), ASXL1 and downstream H3K4me3, H3K27me3 and HOXA9 expression and inhibited EZH2 and H3K27me3 nuclear translocation. Curcumin also showed anti-cancer effects in a xenograft mouse model and reduced EZH2, H3K4me3 and H3K27me3 in vivo. EZH2 knockdown can reduce the H3K27me3 levels and induce curcumin resistance in vitro but it attenuates leukemic transformation in vivo. These findings provide the potential molecular mechanism of curcumin as a therapeutic agent for MDS.

Keywords:

Myelodysplastic syndrome, curcumin, EZH2, H3K27me3, HOXA9

Affiliation:

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030



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