PMID- 23806212
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20211203
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 272
IP  - 2
DP  - 2013 Oct 15
TI  - Trichodermin induces cell apoptosis through mitochondrial dysfunction and 
      endoplasmic reticulum stress in human chondrosarcoma cells.
PG  - 335-44
LID - S0041-008X(13)00283-4 [pii]
LID - 10.1016/j.taap.2013.06.010 [doi]
AB  - 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.
CI  - Copyright (c) 2013. Published by Elsevier Inc.
FAU - Su, Chen-Ming
AU  - Su CM
AD  - Graduate Institute of Basic Medical Science, China Medical University, Taichung, 
      Taiwan.
FAU - Wang, Shih-Wei
AU  - Wang SW
FAU - Lee, Tzong-Huei
AU  - Lee TH
FAU - Tzeng, Wen-Pei
AU  - Tzeng WP
FAU - Hsiao, Che-Jen
AU  - Hsiao CJ
FAU - Liu, Shih-Chia
AU  - Liu SC
FAU - Tang, Chih-Hsin
AU  - Tang CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130624
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Hspa5 protein, mouse)
RN  - 4682-50-2 (Trichodermin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/*pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Bone Neoplasms/*drug therapy/metabolism/pathology
MH  - Calcium/metabolism
MH  - Cell Culture Techniques
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chondrosarcoma/*drug therapy/metabolism/pathology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Humans
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Mice, Nude
MH  - Mitochondria/*drug effects/metabolism/pathology
MH  - Trichodermin/administration & dosage/*pharmacology/therapeutic use
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Apoptosis
OT  - Chondrosarcoma
OT  - Endoplasmic reticulum (ER) stress
OT  - Mitochondrial dysfunction
OT  - Trichodermin
EDAT- 2013/06/29 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/06/29 06:00
PHST- 2013/03/21 00:00 [received]
PHST- 2013/06/11 00:00 [revised]
PHST- 2013/06/11 00:00 [accepted]
PHST- 2013/06/29 06:00 [entrez]
PHST- 2013/06/29 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - S0041-008X(13)00283-4 [pii]
AID - 10.1016/j.taap.2013.06.010 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2013 Oct 15;272(2):335-44. doi: 
      10.1016/j.taap.2013.06.010. Epub 2013 Jun 24.