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

Free Radical Biology & Medicine
Wai-Leng Lee, Lie-Fen Shyur

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 ...Continue Reading

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Citations

May 13, 2015·Physiology and Molecular Biology of Plants : an International Journal of Functional Plant Biology·Jyothi Abraham, T Dennis Thomas
Jan 24, 2014·Oxidative Medicine and Cellular Longevity·Wai-Leng LeeLie-Fen Shyur
Feb 7, 2014·Natural Product Research·Sachin M Hiradeve, Vinod D Rangari
Oct 30, 2018·Journal of Cellular Physiology·Jiaxin ChenXiaotong Hu
Apr 9, 2016·Molecular Oncology·Kyoko Nakagawa-GotoLie-Fen Shyur

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