Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and mitochondria-dependent pathways

Chueh,Fu-Shin; Hsiao,Yung-Ting; Chang,Shu-Jen; Wu,Ping-Ping; Yang,Jai-Sing; Lin,Jen-Jyh; Chung,Jing-Gung; Lai,Tung-Yuan

doi:10.3892/or.2012.2029

Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and mitochondria-dependent pathways

Authors:
- Fu-Shin Chueh
- Yung-Ting Hsiao
- Shu-Jen Chang
- Ping-Ping Wu
- Jai-Sing Yang
- Jen-Jyh Lin
- Jing-Gung Chung
- Tung-Yuan Lai
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Affiliations: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C., School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung, Taiwan, R.O.C., Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C., Department of Traditional Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C.
Published online on: September 12, 2012 https://doi.org/10.3892/or.2012.2029
Pages: 2069-2076

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Abstract

Leukemia, one of the causes of cancer-related death in humans, is an aggressive malignancy via the rapid growth of abnormal white blood cells. The aim of this study was to determine the anti-leukemia effect of glycyrrhizic acid (GA) on a mouse leukemia cell line, WEHI-3. GA, an active compound in Glycyrrhiza glabra, has been proven to induce cytotoxic effects in many cancer cell lines. In the current study, we investigated the effects of GA in mouse leukemia cells in vitro. The results indicated that GA induced morphological changes, G0/G1 phase arrest, apoptosis and DNA damage in WEHI-3 cells as determined by phase contrast microscopy, DAPI-staining, flow cytometry and comet assay. The results from the flow cytometric assay showed that GA increased ROS levels, reduced the mitochondrial membrane potential (ΔΨm) and stimulated caspase-3 activity in WEHI-3 cells. GA regulated the intrinsic and extrinsic apoptosis-associated protein expression which was determined by western blotting. In addition, endoplasmic reticulum (ER) stress responses were observed in GA-treated WEHI-3 cells. GA promoted the trafficking of apoptosis-inducing factor (AIF), cytochrome c and endonuclease G (Endo G) in WEHI-3 cells. Based on this evidence, GA-triggered apoptosis occurs through the death receptor, mitochondria-mediated and ER stress multiple signaling pathways.

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