Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/917519

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Title
Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78
Author/Creator
Mhaidat, Nizar M.;  Alali, Feras Q.;  Matalqah, Sina M.;  Matalka, Ismail I.;  Jaradat, Saied A.;  Al-Sawalha, Nour A.;  Thorne, Rick F.
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
Here we report that paclitaxel induces variable degrees of apoptosis in human colorectal cancer cells. Paclitaxel induces multiple arms of the endoplasmic reticulum stress response, including upregulation of the 78-kDa glucose-regulatory protein (GRP78) and eukaryotic initiation factor [alpha] phosphorylation. Inhibition of the MEK/ERK pathway sensitized colorectal cancer cells to paclitaxel-induced apoptosis. A similar result was obtained by the inhibition of GRP78 using small interfering RNA molecules. Knockdown of MEK resulted in a significant downregulation of paclitaxel-induced upregulation of GRP78 indicating that activation of GRP78 is a downstream event of MEK/ERK pathway activation. These results indicate that GRP78 might be a novel mechanism underlying the resistance of colorectal cancer cells to microtubule-targeting drugs. A combination of compounds capable of suppressing GRP78 might be a golden approach for improving the effectiveness of taxanes.
Relation
Anti-Cancer Drugs Vol. 20, Issue 7, p. 601-606
Publisher Link
http://dx.doi.org/10.1097/CAD.0b013e32832e3120
Date
2009
Publisher
Lippincott Williams & Wilkins
Keyword(s)
apoptosis;  colon cancer;  78-kDa glucose-regulatory protein;  paclitaxel;  unfolded protein response
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/917519
Identifier
ISSN:0959-4973
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Subject
"Anti-Cancer Drugs"
 
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