Induction of human leukemia U937 cell apoptosis by an ethanol extract of Dendropanax morbifera Lev. through the caspase-dependent pathway

Lee,Joon   Wοο; Park,Cheol; Han,Min  Hο; Hong,Su  Hyun; Lee,Tae  Kyung; Lee,Shin  Hwa; Kim,Gi-Young; Choi,Yung  Hyun

doi:10.3892/or.2013.2542

Induction of human leukemia U937 cell apoptosis by an ethanol extract of Dendropanax morbifera Lev. through the caspase-dependent pathway

Authors:
- Joon Wοο Lee
- Cheol Park
- Min Hο Han
- Su Hyun Hong
- Tae Kyung Lee
- Shin Hwa Lee
- Gi-Young Kim
- Yung Hyun Choi
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Affiliations: Bunpo School, Nam-gu, Busan 608-832, Republic of Korea, Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea, Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea, Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614‑052, Republic of Korea, Department of Biology, New York University, New York, NY 10012, USA, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea
Published online on: June 19, 2013 https://doi.org/10.3892/or.2013.2542
Pages: 1231-1238

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Abstract

Dendropanax morbifera Leveille is found throughout southwestern Korea, and has been used in traditional medicine for various diseases, such as migraine headache, infectious diseases, skin diseases and dysmenorrhea. However, the molecular mechanisms of D. morbifera concerning its biochemical actions in cancer have not yet been clearly elucidated. In the present study, we investigated the pro-apoptotic effects of an ethanol extract of D. morbifera stem bark (EEDM) on human leukemia U937 cells. EEDM markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis. EEDM-induced apoptosis in U937 cells was associated with the upregulation of death receptor-related protein levels and downregulation of anti-apoptotic IAP family proteins. The increase in apoptosis was also associated with proteolytic activation of caspase-8, -9 and -3, inhibition of anti‑apoptotic Bcl-2 and Bcl-xL expression, Bid cleavage, and loss of MMP suggesting that apoptosis of U937 cells induced by EEDM was through the extrinsic and intrinsic pathways. However, a pan-caspase inhibitor, z-VED-fmk, significantly inhibited EEDM-induced U937 cell apoptosis indicating that the caspases were key regulators of apoptosis in response to EEDM in U937 cells. Our data suggest that D. morbifera may be a potential anticancer agent for cancer treatment.

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