2. Academic Validation
  3. The new mitochondrial uncoupler BAM15 induces ROS production for treatment of acute myeloid leukemia

The new mitochondrial uncoupler BAM15 induces ROS production for treatment of acute myeloid leukemia

  • Biochem Pharmacol. 2022 Apr;198:114948. doi: 10.1016/j.bcp.2022.114948.
Zhen Xing Gao 1,  Ze Long Cui 1,  Min Ran Zhou 1,  Yue Fu 2,  Fen Liu 3,  Lu Zhang 1,  Sai Ma 4,  Chun Yan Chen 5
Affiliations

Affiliations

  • 1 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 3 Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 4 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: masai1233@126.com.cn.
  • 5 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: chency@sdu.edu.cn.
PMID: 35192847 DOI: 10.1016/j.bcp.2022.114948
Abstract

Acute myeloid leukemia (AML) is a malignant proliferative disease of myeloid hematopoietic origin and cannot be treated appropriately at present. This is due to the fact that leukemia cells are not sensitive to some of the traditional chemotherapy drugs. Or some chemotherapeutic drugs are too toxic to normal cells, affecting their wide clinical application. In this study, we identified BAM15 as a novel mitochondrial uncoupling agent by screening a library of small molecule compounds that inhibit AML cell activity. BAM15 significantly inhibited proliferation and promoted Apoptosis in AML cells while at the same time being less cytotoxic to normal cells. The mechanism may be related to the disturbance of the ROS production balance. In vivo investigations revealed that BAM15 effectively suppressed AML progression and prolonged the survival time of mice. In addition, we found that BAM15 can be used in combination with cytarabine to enhance its anti-cancer activity and inhibit the activity of primary cells in AML. Therefore, we identified BAM15 as a potential drug candidate for the treatment of AML.

Keywords

Apoptosis; BAM15; Leukemia; Primary cells; Proliferation; ROS.

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