Honokiol induces cell apoptosis in human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress

Chen, Ying-Ju; Wu, Chien-Lin; Liu, Ju-Fang; Fong, Yi-Chin; Hsu, Sheng-Feng; Li, Te-Mao; Su, Yi-Chang; Liu, Shing-Hwa; Tang, Chih-Hsin

doi:10.1016/j.canlet.2009.08.032

« Previous Next »Cancer Letters
Volume 291, Issue 1 , Pages 20-30, 1 May 2010

Honokiol induces cell apoptosis in human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress

Ying-Ju Chen
- Institute of Toxicology, National Taiwan University, Taipei, Taiwan, ROC
- These authors contributed equally to this work.
Chien-Lin Wu
- Department of Physical Medicine and Rehabilitation, Changhua Christian Hospital, Changhua, Taiwan, ROC
Ju-Fang Liu
- Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC
Yi-Chin Fong
- School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC
- Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC
- Department of Orthopaedic, China Medical University Hospital, Taichung, Taiwan, ROC
- These authors contributed equally to this work.
Sheng-Feng Hsu
- Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan, ROC
Te-Mao Li
- Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan, ROC
Yi-Chang Su
- Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC
Shing-Hwa Liu
- Institute of Toxicology, National Taiwan University, Taipei, Taiwan, ROC
- Corresponding authors. Address: Department of Pharmacology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan, ROC. Tel.: +886 4 22053366x2228; fax: +886 4 22053764 (C.-H. Tang).
Chih-Hsin Tang
- Department of Pharmacology, China Medical University, Taichung, Taiwan, ROC
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC
- Corresponding authors. Address: Department of Pharmacology, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan, ROC. Tel.: +886 4 22053366x2228; fax: +886 4 22053764 (C.-H. Tang).

Received 16 May 2009; received in revised form 25 August 2009; accepted 25 August 2009. published online 02 November 2009.

Abstract

Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. In the present study, we investigated the anti-cancer effect of a honokiol, an active component isolated and purified from the Magnolia officinalis in human chondrosarcoma cells. Honokiol-induced cell apoptosis in human chondrosarcoma cell lines (including: JJ012 and SW1353) but not primary chondrocytes. Honokiol also induces upregulation of Bax and Bak, downregulation of Bcl-XL and dysfunction of mitochondria in chondrosarcoma cells. Honokiol triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol-calcium levels. We also found that honokiol increased the expression and activities of glucose-regulated protein 78 (GRP78) and calpain. Transfection of cells with GRP78 or calpain siRNA reduced honokiol-mediated cell apoptosis in JJ012 cells. Importantly, animal studies have revealed a dramatic 53% reduction in tumor volume after 21days of treatment. This study demonstrates that honokiol may be a novel anti-cancer agent targeting chondrosarcoma cells.