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Research Paper|Volume 14, Issue 17|pp 7109—7125

Realgar (As4S4), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro

Zonghong Li1, Ruiming Zhang2, Xuewei Yin1, Nana Li3, Siyuan Cui4, Teng Wang1, Xing Tan1, Mingyue Shen5, Yun Guo6, Jinxin Wang4, Dadong Guo7, Ruirong Xu4
  • 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province, China
  • 2Department of Hematology, Linyi Hospital of Traditional Chinese Medicine, Linyi 276002, Shandong Province, China
  • 3Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
  • 4Department of Hematology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province, China
  • 5College of Pharmacy, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • 6Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
  • 7Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Shandong Academy of Eye Disease Prevention and Therapy, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province, China
* Equal contribution and share first authorship
Received: May 6, 2022Accepted: September 1, 2022Published: September 12, 2022
https://doi.org/10.18632/aging.204281

Copyright: © 2022 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML) characterized by the proliferation of abnormal promyelocytes. Realgar, a Chinese medicine containing arsenic, can be taken orally. Traditional Chinese medicine physicians have employed realgar to treat APL for over a thousand years. Therefore, realgar may be a promising candidate for the treatment of APL. Nevertheless, the underlying mechanism behind realgar therapy is largely unclear. The present study aimed to investigate the effect of realgar on cell death in the APL cell line (NB4) in vitro and to elucidate the underlying mechanism. In this study, after APL cells were treated with different concentrations of realgar, the cell survival rate, apoptotic assay, morphological changes, ATP levels and cell cycle arrest were assessed. The expression of Bcl-2, Bax, Cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) at the mRNA and protein levels were also measured by immunofluorescence, quantitative PCR (qPCR) and Western blotting. We found that realgar could significantly inhibit APL cell proliferation and cell death in a time- and dose-dependent manner. Realgar effectively decreased the ATP levels in APL cells. Realgar also induced APL cell cycle arrest at the S and G2/M phases. Following realgar treatment, the mRNA and protein levels of Bcl-2 were significantly downregulated, whereas the levels of Bax, Cyt-C, and AIF were significantly upregulated. In summary, realgar can induce APL cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway, suggesting that realgar may be an effective therapeutic for APL.