Activation of NAG-1 via JNK signaling revealed an isochaihulactone-triggered cell death in human LNCaP prostate cancer cells

BMC Cancer

Research Article

Shinn-Zong Lin¹  Hsueh-Hui Yang²  Sung-Ying Huang³  Yi-Lin Chen⁴  Sheng-Chun Chiu⁵  Mei-Jen Wang⁵  Cheng-Yoong Pang⁵  Horng-Jyh Harn⁶  Shee-Ping Chen⁷ 

[1] Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan;Department of Medical Research, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;Department of Ophthalmology, Mackay Memorial Hospital, Hsinchu, Taiwan;Graduate Institute of Biotechnology, National Ilan University, Ilan, Taiwan;Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan;Department of Medical Research, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;Pathology Department, China Medical University, Taichung, Taiwan;Tzu-Chi Stem Cell Centre, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;

关键词: A549 Cell;    LNCaP Cell;    Human Prostate Cancer Cell Line;    Human Lung Carcinoma Cell Line;    Human LNCaP Prostate Cancer Cell;   

DOI  :  10.1186/1471-2407-11-146

 received in 2010-07-14, accepted in 2011-04-20,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundWe explored the mechanisms of cell death induced by isochaihulactone treatment in LNCaP cells.MethodsLNCaP cells were treated with isochaihulactone and growth inhibition was assessed. Cell cycle profiles after isochaihulactone treatment were determined by flow cytometry. Expression levels of cell cycle regulatory proteins, caspase 9, caspase 3, and PARP were determined after isochaihulactone treatment. Signaling pathway was verified by inhibitors pre-treatment. Expression levels of early growth response gene 1 (EGR-1) and nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) were determined to investigate their role in LNCaP cell death. NAG-1 expression was knocked down by si-NAG-1 siRNA transfection. Rate of cell death and proliferation were obtained by MTT assay.ResultsIsochaihulactone caused cell cycle arrest at G2/M phase in LNCaP cells, which was correlated with an increase of p53 and p21 levels and downregulation of the checkpoint proteins cdc25c, cyclin B1, and cdc2. Bcl-2 phosphorylation and caspase activation were also observed. Isochaihulactone induced phosphorylation of c-Jun-N-terminal kinase (JNK), and JNK inhibitor partially reduced isochaihulactone-induced cell death. Isochaihulactone also induced the expressions of EGR-1 and NAG-1. Expression of NAG-1 was reduced by JNK inhibitor, and knocking down of NAG-1 inhibited isochaihulactone-induced cell death.ConclusionsIsochaihulactone apparently induces G2/M cell cycle arrest via downregulation of cyclin B1 and cdc2, and induces cellular death by upregulation of NAG-1 via JNK activation in LNCaP cells.

【 授权许可】

Unknown   
© Chiu et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.