Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells
| Autor: | Shih-Chia Liu, Chen-Ming Su, Tzong-Huei Lee, Chih-Hsin Tang, Shih-Wei Wang, Che-Jen Hsiao, Wen-Pei Tzeng |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology medicine.medical_specialty Cell Survival Trichodermin Cell Culture Techniques Chondrosarcoma Mice Nude Antineoplastic Agents Apoptosis Bone Neoplasms Biology Mitochondrion Toxicology Mice chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor medicine Animals Humans Endoplasmic Reticulum Chaperone BiP Membrane Potential Mitochondrial Pharmacology TUNEL assay Endoplasmic reticulum Endoplasmic Reticulum Stress medicine.disease Xenograft Model Antitumor Assays Mitochondria Cell biology chemistry Unfolded protein response Calcium |
| Zdroj: | Toxicology and Applied Pharmacology. 272:335-344 |
| ISSN: | 0041-008X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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