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

Chen Ming Su, Shih Wei Wang, Zong-Huei Li, Wen Pei Tzeng, Che Jen Hsiao, Shih Chia Liu, Chih Hsin Tang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalToxicology and Applied Pharmacology
Volume272
Issue number2
DOIs
Publication statusPublished - Oct 15 2013

Keywords

  • Apoptosis
  • Chondrosarcoma
  • Endoplasmic reticulum (ER) stress
  • Mitochondrial dysfunction
  • Trichodermin

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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