Journal
CANCER LETTERS
Volume 291, Issue 1, Pages 20-30Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.08.032
Keywords
Honokiol; Chondrosarcoma; GRP78; ER
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Funding
- National Science Council of Taiwan [96-2320-B-039-028-MY3, 97-2815-C-039-014-B]
- China Medical University [CMU97-180]
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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 21 days of treatment. This study demonstrates that honokiol may be a novel anti-cancer agent targeting chondrosarcoma cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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