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Research Paper
Role of MRIT/cFLIP in Protection Against Chemotherapy-Induced Apoptosis
Hittu Matta, Michael T. Eby, Adi F. Gazdar and Preet M. Chaudhary
volume 1 | issue 6
november/december 2002Pages: 652-660
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MRIT (Mach-related inducer of toxicity)/cFLIP (cellular FADD like interlukin1-b converting enzyme inhibitory protein) is a proteolytically inactive structural homologue of caspase-8, which is known to protect against death receptors-induced apoptosis by blocking the activation of caspase-8. We have observed that exogenous expression of MRITa1/cFLIPL isoform also protects against cell death induced by a diverse group of chemotherapeutic drugs with different mechanisms of action, including doxorubicin, etoposide, cytosine arabinoside, daunorubicin, chlorambucil and cisplatin. However, MRITa1/cFLIPL failed to protect against apoptosis induced by paclitaxel and vincristine, two microtubule-damaging agents. Although MRITa1/cFLIPL protects against chemotherapy-induced apoptosis in both solid tumor and hematopoietic cell lines, this effect was more pronounced in the former. MRITa1/cFLIPL expression is decreased during drug-induced apoptosis and exogenous expression of MRITa1/cFLIPL delays the activation of caspase-8 and -3 during drug- induced apoptosis. These results suggest that MRITa1/cFLIPL may be an important determinant of both death receptor- and chemotherapy-induced apoptosis and strategies aimed at downregulating its expression deserve further study as a way to overcome multidrug resistance to cancer therapy.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.