Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification

Tian, Tian; Li, Jiajun; Li, Yizhuo; Lu, Yun-Xin; Tang, Yan-Lai; Wang, Hua; Zheng, Fufu; Shi, Dingbo; Long, Qian; Chen, Miao; Garcia-Manero, Guillermo; Hu, Yumin; Qin, Lijun; Deng, Wuguo

doi:10.7150/thno.34327

Nanotheranostics 2025; 9(1): 38-51. Full text PDF PubMed PMC

Nanotheranostics 2025; 9(1): 31-37. Full text PDF PubMed PMC

Nanotheranostics

International Journal of Biological Sciences

International Journal of Medical Sciences

Journal of Cancer

open access Global reach, higher impact

Full Text | PDF

Theranostics 2019; 9(13):3768-3779. doi:10.7150/thno.34327 This issue Cite

Research Paper

Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification

Tian Tian^1*, Jiajun Li^1*, Yizhuo Li^1*, Yun-Xin Lu^1*, Yan-Lai Tang³, Hua Wang¹, Fufu Zheng³, Dingbo Shi¹, Qian Long¹, Miao Chen¹, Guillermo Garcia-Manero⁴, Yumin Hu^1✉, Lijun Qin^2✉, Wuguo Deng^1✉

1. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
2. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510000, China.
3. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
4. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
*These authors contributed equally to this article.

Citation:

Tian T, Li J, Li Y, Lu YX, Tang YL, Wang H, Zheng F, Shi D, Long Q, Chen M, Garcia-Manero G, Hu Y, Qin L, Deng W. Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification. Theranostics 2019; 9(13):3768-3779. doi:10.7150/thno.34327. https://www.thno.org/v09p3768.htm

Other styles

Abstract

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis in FLT3/ITD-positive leukemia cells. Mechanistically, melatonin preferentially causes overproduction of reactive oxygen species (ROS) and ultimately massive cell death in FLT3-ITD AML cells. Moreover, melatonin significantly enhances the cytotoxicity induced by the FLT3 tyrosine kinase inhibitor sorafenib in AML cells with FLT3/ITD through redox modification. Importantly, combination of melatonin and sorafenib exhibited highly synergistic therapeutic activity in MV4-11 xenografts and a murine model bearing FLT3/ITD leukemia.

Conclusion: This study indicates that melatonin, alone or in combination with sorafenib, has potential to improve the therapeutic outcome of AML patients with FLT3-ITD mutation that merits further investigation.

Keywords: Melatonin, Sorafenib, FLT3-ITD, Leukemia, Redox modification

Citation styles

APA

Tian, T., Li, J., Li, Y., Lu, Y.X., Tang, Y.L., Wang, H., Zheng, F., Shi, D., Long, Q., Chen, M., Garcia-Manero, G., Hu, Y., Qin, L., Deng, W. (2019). Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification. Theranostics, 9(13), 3768-3779. https://doi.org/10.7150/thno.34327.

ACS

Tian, T.; Li, J.; Li, Y.; Lu, Y.X.; Tang, Y.L.; Wang, H.; Zheng, F.; Shi, D.; Long, Q.; Chen, M.; Garcia-Manero, G.; Hu, Y.; Qin, L.; Deng, W. Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification. Theranostics 2019, 9 (13), 3768-3779. DOI: 10.7150/thno.34327.

NLM

CSE

Tian T, Li J, Li Y, Lu YX, Tang YL, Wang H, Zheng F, Shi D, Long Q, Chen M, Garcia-Manero G, Hu Y, Qin L, Deng W. 2019. Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification. Theranostics. 9(13):3768-3779.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.