ReferenceID 3552

Deoxyelephantopin impedes mammary adenocarcinoma cell motility by inhibiting calpain-mediated adhesion dynamics and inducing reactive oxygen species and aggresome formation

Free Radic Biol Med

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 studi

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Reference Id
3552
Evidence Id
20142
Core Evidence Id
20142
Source Reference Id
413
Herb2 Reference Id
HBREF000725
Subject Paper Key
HBIN023361_22342517
Pubmed Id
22342517
Doi
10.1016/j.freeradbiomed.2012.01.020
Paper Title
Deoxyelephantopin impedes mammary adenocarcinoma cell motility by inhibiting calpain-mediated adhesion dynamics and inducing reactive oxygen species and aggresome formation
Paper Abstract
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.
Journal
Free Radic Biol Med
Publish Year
2012
Experiment Subject
mammary adenocarcinoma ts/a cells
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Deoxyelephantopin impedes mammary adenocarcinoma cell motility by inhibiting calpain-mediated adhesion dynamics and inducing reactive oxygen species and aggresome formation
Bilingual Status
semi_complete