1. Academic Validation
  2. Tubeimoside I induces mitophagy by activating the PINK1/Parkin/Mfn2 signaling pathway in acute myeloid leukemia cells

Tubeimoside I induces mitophagy by activating the PINK1/Parkin/Mfn2 signaling pathway in acute myeloid leukemia cells

  • Transl Oncol. 2025 Mar 19:55:102355. doi: 10.1016/j.tranon.2025.102355.
Jing Xu 1 Fanggang Ren 2 Jinjuan Wang 3 Jianbing Liu 3 Xiaohua Cui 3 Jianqing Hao 3 Wanfang Yang 4 Yaofang Zhang 2 Dongmin Cao 5 Li Li 6 Hongwei Wang 7
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan 030001, China.
  • 2 Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
  • 3 School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China.
  • 4 School of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
  • 5 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Zhongshan 528437, China. Electronic address: caodongmin012345@163.com.
  • 6 School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan 030001, China. Electronic address: lili_5076@sxmu.edu.cn.
  • 7 Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China; School of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, China. Electronic address: wanghw68@sxmu.edu.cn.
Abstract

Acute myeloid leukemia (AML) is the most prevalent kind of acute leukemia in adults. Despite the availability of new targeted therapies, AML remains connected with a poor prognosis and decreased rate of survival. Tubeimoside I (TBMS1), a critical compound extracted from Bolbostemma paniculatum, has demonstrated potential Anticancer effects in lung and colorectal cancers. Nevertheless, the TBMS1 Anticancer pathway against AML is still elusive. This study aimed to explore the potential role of TBMS1 in anti-AML and its molecular mechanism. In vitro, TBMS1 treatment suppressed AML cells proliferation, induced Apoptosis, and mitochondrial damage, and elevated ROS levels. Network pharmacological analysis suggested, and subsequent studies confirmed, that TBMS1 induced Mitophagy in AML cells by modulating the PINK1/Parkin/Mfnh2 signaling pathway, an effect that was effectively reversed following PINK1 knockdown. In vivo, TBMS1 treatment suppressed the proliferation of AML cells after 21 days, improved the survival rates of nude mice, and showed no evident organ toxicity. These evidences suggest that TBMS1 may have significant therapeutic potential in treating AML.

Keywords

Acute myeloid leukemia; Mitophagy; PINK1/Parkin/Mfn2 signaling pathway; Tubeimoside I.

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