RU486, a glucocorticoid receptor antagonist, induces apoptosis in U937 human lymphoma cells through reduction in mitochondrial membrane potential and activation of p38 MAPK

Jang,Ji Hoon; Woo,Seon Min; Um,Hee Jung; Park,Eun Jung; Min,Kyoung-Jin; Lee,Tae-Jin; Kim,Sang Hyun; Choi,Yung Hyun; Kwon,Taeg Kyu

doi:10.3892/or.2013.2432

RU486, a glucocorticoid receptor antagonist, induces apoptosis in U937 human lymphoma cells through reduction in mitochondrial membrane potential and activation of p38 MAPK

Authors:
- Ji Hoon Jang
- Seon Min Woo
- Hee Jung Um
- Eun Jung Park
- Kyoung-Jin Min
- Tae-Jin Lee
- Sang Hyun Kim
- Yung Hyun Choi
- Taeg Kyu Kwon
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Affiliations: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, Republic of Korea, Department of Anatomy, College of Medicine, Yeungnam University, Daegu, Republic of Korea, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Republic of Korea
Published online on: April 26, 2013 https://doi.org/10.3892/or.2013.2432
Pages: 506-512

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Abstract

RU486 (mifepristone) exerts an anticancer effect on cancer cells via induction of apoptosis. However, the molecular mechanisms are not fully understood. Here, we investigated the effect of RU486 on the apoptosis of U937 human leukemia cells. RU486 markedly increased apoptosis in U937 cells as well as in MDA231 human breast carcinoma, A549 human lung adenocarcinoma epithelial and HCT116 human colorectal carcinoma cells. RU486 increased dose-dependent release of mitochondrial cytochrome c, and reduced the mitochondrial membrane potential (MMP, Δψm) in RU486‑treated U937 cells. We also found that overexpression of Bcl-2 completely blocked RU486-mediated apoptosis. However, reactive oxygen species signaling had no effect on RU486‑induced apoptosis. RU486 increased the phosphorylation of p38 MAPK and JNK, but p38 MAPK only was associated with RU486-mediated apoptosis. Taken together, RU486 induces apoptosis through reduction in the mitochondrial membrane potential and activation of p38 MAPK in U937 human leukemia cells.

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