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Title: Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress ismore » involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [1] ;  [7] ;  [7]
  1. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China)
  2. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China)
  3. Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China)
  4. Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China)
  5. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)
  6. Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China)
  7. (China)
Publication Date:
OSTI Identifier:
22285426
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 272; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CALCIUM; CHEMOTHERAPY; ENDOPLASMIC RETICULUM; MITOCHONDRIA; NEOPLASMS; PROTEINS; SKELETON; STRESSES