Honokiol induces cell apoptosis in human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress.
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.
Chen
Ying-Ju
YJ
Institute of Toxicology, National Taiwan University, Taipei, ROC.
Wu
Chien-Lin
CL
Liu
Ju-Fang
JF
Fong
Yi-Chin
YC
Hsu
Sheng-Feng
SF
Li
Te-Mao
TM
Su
Yi-Chang
YC
Liu
Shing-Hwa
SH
Tang
Chih-Hsin
CH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D002118:Calcium; D002154:Calpain; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D017705:Lignans; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols