Honokiol induces cell apoptosis in human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress
Journal
Cancer Letters
Journal Volume
291
Journal Issue
1
Pages
20-30
Date Issued
2010
Author(s)
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 21 days of treatment. This study demonstrates that honokiol may be a novel anti-cancer agent targeting chondrosarcoma cells. ? 2009 Elsevier Ireland Ltd. All rights reserved.
Subjects
Chondrosarcoma; ER; GRP78; Honokiol
SDGs
Other Subjects
calcium; calpain; glucose regulated protein 78; honokiol; protein Bak; protein Bax; protein bcl xl; small interfering RNA; animal experiment; animal model; antineoplastic activity; apoptosis; article; cancer size; cartilage cell; chondrosarcoma; controlled study; cytosol; disorders of mitochondrial functions; down regulation; drug effect; drug isolation; drug mechanism; drug targeting; endoplasmic reticulum stress; genetic transfection; human; human cell; magnolia officinalis; Magnoliaceae; nonhuman; priority journal; protein expression; sarcoma cell; upregulation; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Bone Neoplasms; Calcium; Calpain; Cell Line, Tumor; Chondrosarcoma; Endoplasmic Reticulum; Heat-Shock Proteins; Humans; Lignans; Male; Mice; Mice, Inbred BALB C; Mitochondria; Xenograft Model Antitumor Assays; Animalia; Magnolia officinalis
Type
journal article