Ai CJ, Chen LJ, Guo LX, Wang YP, Zhao ZY. Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction. World J Stem Cells 2024; 16(4): 444-458 [PMID: 38690512 DOI: 10.4252/wjsc.v16.i4.444]
Corresponding Author of This Article
Zi-Yi Zhao, PhD, Professor, Central Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Shi-er-qiao Road, Chengdu 641000, Sichuan Province, China. zhaoziyi@cdutcm.edu.cn
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Cheng-Jin Ai, Ling-Juan Chen, Li-Xuan Guo, Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 641000, Sichuan Province, China
Ya-Ping Wang, Department of Ophthalmology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 641000, Sichuan Province, China
Zi-Yi Zhao, Central Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 641000, Sichuan Province, China
Zi-Yi Zhao, Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu University of Traditional Chinese Medicine, Chengdu 641000, Sichuan Province, China
Co-first authors: Cheng-Jin Ai and Ling-Juan Chen.
Author contributions: Ai CJ and Zhao ZY designed the experiments and wrote manuscript; Ai CJ, Chen LJ, Guo LX, and Wang YP performed molecular-related experiments in this study; Ai CJ and Chen LJ performed experiments on processing cells, and they are co-first authors of this manuscript; Zhao ZY is responsible for data collection and performed statistical analysis and revised manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: No human or animal subjects was involved in this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zi-Yi Zhao, PhD, Professor, Central Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Shi-er-qiao Road, Chengdu 641000, Sichuan Province, China. zhaoziyi@cdutcm.edu.cn
Received: January 15, 2024 Peer-review started: January 15, 2024 First decision: January 29, 2024 Revised: February 11, 2024 Accepted: March 14, 2024 Article in press: March 14, 2024 Published online: April 26, 2024 Processing time: 100 Days and 13.2 Hours
ARTICLE HIGHLIGHTS
Research background
The presence of leukemia stem cells (LSCs) is one of the major contributors of poor prognosis and outcome of myeloid leukemia. By considering the anti-chemoagent property of LSCs, it is still a major challenge of developing chemoagent targeting to this sub-population of acute myeloid leukemia (AML).
Research motivation
The subpopulation of AML is characterized by remarkable anti-agent property, which leads to poor therapeutic effects. Instead of searching chemoagent exerting cytotoxic effect against LSCs, developing chemoagent or molecule exerting anti-stemness might be a promising strategy.
Research objectives
We aimed to evaluate the effects of gossypol acetic acid (GAA) on stemness of LSCs. We also evaluated the malignent behaviors after GAA treatment.
Research methods
LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured.
Research results
GAA treatment decreased LRPPRC, and thus inhibiting interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling. As a result, GAA treatment decreased stemness and enhanced chemosensitivity in LSCs.
Research conclusions
Our results indicate that GAA might overcome the bone marrow microenvironment protective effect and be considered as a novel and effective combination therapy for AML.
Research perspectives
It is worth investigating how GAA results degradation of LRPPRC. Meanwhile, it is worth to evaluate the effects of GAA in AML mice model to evaluate the therapeutic effect in vivo.
