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eCAM Advance Access published online on October 27, 2009
eCAM, doi:10.1093/ecam/nep176
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Agaricus blazei Extract Induces Apoptosis through ROS-dependent JNK Activation Involving the Mitochondrial Pathway and Suppression of Constitutive NF-{kappa}B in THP-1 Cells

Mun-Ock Kim1, Dong-Oh Moon1, Jin Myung Jung2, Won Sup Lee3, Yung Hyun Choi4 and Gi-Young Kim1

1Laboratory of Immunobiology, Department of Marine Life Science, Jeju National University, Jeju, Republic of Korea, 2Department of Neurosurgery, 3Department of Internal Medicine, Institute of Health Science, Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, Republic of Korea and 4Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Republic of Korea

Agaricus blazei is widely accepted as a traditional medicinal mushroom, and it has been known to exhibit immunostimulatory and anti-cancer activity. However, the apoptotic mechanism in cancer cells is poorly understood. In this study, we have investigated whether A. blazei extract (ABE) exerts antiproliferative and apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced apoptosis is associated with the mitochondrial pathway, which is mediated by reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase (JNK) activation. In addition, the ABE treatment resulted in the accumulation of cytochrome c in the cytoplasm, an increase in caspase activity, and an upregulation of Bax and Bad. With those results in mind, we found that ABE decreases constitutive NF-{kappa}B activation and NF-{kappa}B-regulated gene products such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent JNK activation and constitutive activated NF-{kappa}B inhibition in THP-1 cells.

Keywords: Agaricus blazei – apoptosis – c-Jun N-terminal kinase – nuclear factor-{kappa}B – reactive oxygen species

For reprints and all correspondence: Prof. Gi-Young Kim, Laboratory of Immunobiology, Department of Marine Life Science, Jeju National University, Jeju, Republic of Korea. Tel: +82-64-754-3427; Fax: +82-64-756-3493; E-mail: immunkim{at}jejunu.ac.kr

Received July 16, 2009; accepted October 3, 2009


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