Abstract:
:MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity, but the effect of melatonin on MLL-r leukemia and the underlying mechanism remain poorly understood. In this study, melatonin inhibited cell proliferation and induced apoptosis by activating the caspase-dependent apoptotic pathway in MLL-r leukemia cells. Mechanistic investigations revealed that melatonin suppressed the expression of hTERT by abrogating the binding activity of RBFOX3 to the hTERT promoter. Melatonin also blocked NF-κB nuclear translocation and suppressed NF-κB binding to the COX-2 promoter, thereby suppressing the expression of COX-2. In addition, clinical samples revealed that melatonin exerts anti-leukemic activity in primary MLL-r leukemia blasts ex vivo. In vivo, the mice treated with melatonin experienced a larger reduction in leukemic burden than the control group in a MLL-r leukemia xenograft mouse model. Collectively, these results suggest that melatonin inhibits MLL-rearranged leukemia through suppressing the RBFOX3/hTERT and NF-κB/COX-2 signaling pathways. Our findings provide new insights into the role of melatonin for MLL-r leukemia treatment.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Tang YL,Sun X,Huang LB,Liu XJ,Qin G,Wang LN,Zhang XL,Ke ZY,Luo JS,Liang C,Peng CJ,Tang WY,Li Y,Huang W,Luo XQ,Deng Wdoi
10.1016/j.canlet.2018.11.037subject
Has Abstractpub_date
2019-02-28 00:00:00pages
167-178eissn
0304-3835issn
1872-7980pii
S0304-3835(18)30703-1journal_volume
443pub_type
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