PMID- 22342517
OWN - NLM
STAT- MEDLINE
DCOM- 20120816
LR  - 20120326
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 52
IP  - 8
DP  - 2012 Apr 15
TI  - Deoxyelephantopin impedes mammary adenocarcinoma cell motility by inhibiting 
      calpain-mediated adhesion dynamics and inducing reactive oxygen species and 
      aggresome formation.
PG  - 1423-36
LID - 10.1016/j.freeradbiomed.2012.01.020 [doi]
AB  - We previously showed that deoxyelephantopin (DET), a plant sesquiterpene lactone, 
      exhibits more profound suppression than paclitaxel (PTX) of lung metastasis of 
      mammary adenocarcinoma TS/A cells in mice. Proteomics studies suggest that DET 
      affects actin cytoskeletal protein networks and downregulates calpain-mediated 
      proteolysis of several actin-associated proteins, whereas PTX mainly interferes 
      with microtubule proteins. Here, DET was observed to significantly deregulate 
      adhesion formation in TS/A cells, probably through inhibition of m-calpain 
      activity. Epithelial growth factor (EGF)-mediated activation of Rho GTPase Rac1 
      and formation of lamellipodia in TS/A cells were remarkably suppressed by DET 
      treatment. Further, DET impaired vesicular trafficking of EGF and induced protein 
      carbonylation and formation of centrosomal aggregates in TS/A cells. DET-induced 
      reactive oxygen species were observed to be the upstream stimulus for the 
      formation of centrosomal ubiquitinated protein aggregates that might subsequently 
      restrict cancer cell motility. PTX, however, caused dramatic morphological 
      changes, interfered with microtubule networking, and moderately inhibited 
      calpain-mediated cytoskeletal and focal adhesion protein cleavage in TS/A cells. 
      This study provides novel mechanistic insights into the pharmacological action of 
      DET against metastatic mammary cell migration and suggests that modulation of 
      oxidative stress might be a potential strategy for treatment of metastatic breast 
      cancer.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Lee, Wai-Leng
AU  - Lee WL
AD  - Molecular and Biological Agricultural Sciences Program, Taiwan International 
      Graduate Program, Taiwan, Republic of China.
FAU - Shyur, Lie-Fen
AU  - Shyur LF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120202
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Actins)
RN  - 0 (Lactones)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes)
RN  - 0 (deoxyelephantopin)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 3.4.22.- (Calpain)
SB  - IM
MH  - Actins/metabolism
MH  - Adenocarcinoma/metabolism/*pathology
MH  - Animals
MH  - Calpain/*antagonists & inhibitors/physiology
MH  - Cell Adhesion/*physiology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Movement/*drug effects
MH  - Cytoskeleton/metabolism
MH  - Fluorescent Antibody Technique
MH  - Focal Adhesion Protein-Tyrosine Kinases/metabolism
MH  - Humans
MH  - Lactones/*pharmacology
MH  - Mammary Neoplasms, Experimental/metabolism/*pathology
MH  - Mice
MH  - Proteolysis
MH  - Reactive Oxygen Species/*metabolism
MH  - Sesquiterpenes/*pharmacology
EDAT- 2012/02/22 06:00
MHDA- 2012/08/17 06:00
CRDT- 2012/02/21 06:00
PHST- 2011/06/18 00:00 [received]
PHST- 2012/01/13 00:00 [revised]
PHST- 2012/01/21 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/08/17 06:00 [medline]
AID - S0891-5849(12)00064-0 [pii]
AID - 10.1016/j.freeradbiomed.2012.01.020 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2012 Apr 15;52(8):1423-36. doi: 
      10.1016/j.freeradbiomed.2012.01.020. Epub 2012 Feb 2.