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Melatonin inhibits MLL-rearranged leukemia via RBFOX3/hTERT and NF-κB/COX-2 signaling pathways.
Tang, Yan-Lai; Sun, Xi; Huang, Li-Bin; Liu, Xiao-Jian; Qin, Ge; Wang, Li-Na; Zhang, Xiao-Li; Ke, Zhi-Yong; Luo, Jie-Si; Liang, Cong; Peng, Chun-Jin; Tang, Wen-Yan; Li, Yu; Huang, Wenlin; Luo, Xue-Qun; Deng, Wuguo.
Afiliación
  • Tang YL; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
  • Sun X; Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • Huang LB; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Liu XJ; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Qin G; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
  • Wang LN; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Zhang XL; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Ke ZY; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Luo JS; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Liang C; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Peng CJ; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Tang WY; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Li Y; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Huang W; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China; State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
  • Luo XQ; Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: l-xuequn@126.com.
  • Deng W; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China; State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China. Electronic address:
Cancer Lett ; 443: 167-178, 2019 02 28.
Article en En | MEDLINE | ID: mdl-30550850
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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transducción de Señal / Leucemia / N-Metiltransferasa de Histona-Lisina / Proteína de la Leucemia Mieloide-Linfoide / Melatonina Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancer Lett Año: 2019 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Transducción de Señal / Leucemia / N-Metiltransferasa de Histona-Lisina / Proteína de la Leucemia Mieloide-Linfoide / Melatonina Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancer Lett Año: 2019 Tipo del documento: Article