The following information was submitted:
Transactions: INTERNATIONAL JOURNAL of BIOLOGY and BIOMEDICAL ENGINEERING
Transactions ID Number: 20-502
Full Name: Nizar Mhaidat
Position: Assistant Professor
Age: ON
Sex: Male
Address: Faculty of Pharmacy, Jordan University of Science & Technology, Irbid, 22110
Country: JORDAN
Tel: +96227201000
Tel prefix:
Fax: +96227201075
E-mail address: nizarm@just.edu.jo
Other E-mails: nizarm_2000@yahoo.com
Title of the Paper: Inhibition of GRP78 sensitizes colorectal cancer cells to paclitaxel-induced apoptosis by activation of caspase-4
Authors as they appear in the Paper: Nizar Mhaidat, Saied Jaradat, Ahmad Aldaher, and Abdulhameed Ghabkari
Email addresses of all the authors: nizarm@just.edu.jo, sjaradat@just.edu.jo, dnaseve@yahoo.com, ghabkari_83@yahoo.com
Number of paper pages: 8
Abstract: Resistance of colorectal cancer cells to paclitaxel-induced apoptosis is largely mediated by the activation of MEK/ERK signalling pathway. Inhibition of MEK/ERK pathway sensitized CRC cells to paclitaxel-induced apoptosis by down-regulation of GRP78. In the present study, we report that induction of apoptosis by paclitaxel when GRP78 is down-regulated involves activation of the caspase cascade. In cells, where GRP78 is inhibited, paclitaxel induced activation of caspase-3, caspase-4, and caspase-9. Caspase-4 seemed to be the apical caspase in that caspase-4 activation occurred before activation of caspase-9 and caspase-3. Moreover, activation of caspase-4 was upstream of the mitochondria and its inhibition led to the inhibition of mitochondrial membrane permeability (MMP) and caspase-9 activation. Furthermore, co-immunoprecipitation studies revealed that GRP78 is physically associated with caspase-4 before and after treatment with paclitaxel. These results indicate!
that GRP78 might be a novel mechanism underlying resistance of CRC cells to microtubule-targeting drugs by binding to and inhibition of caspase-4. Combination of compounds capable of suppressing GRP78 might be a golden approach for improving the effectiveness of taxanes in treatment of CRC.
Keywords: Apoptosis, Colorectal Cancer, Grp78, Paclitaxel, Upr.
EXTENSION of the file: .doc
Special (Invited) Session: Sensitization of human colorectal cancer cells to paclitaxel-induced apoptosis by inhibition of MEK/ERK pathway is caspase-4 dependent
Organizer of the Session: 650-316
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