BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

Free Newsletters
My Subscriptions

News by Subject
News by Disease
News by Date
Search News
Post Your News

Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Pharm Country
  Bio NC
  Southern Pharm
  BioCanada East
  C2C Services & Suppliers™


Company Profiles

Research Store

Research Events
Post an Event
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Biochemistry - Hematology - Oncology

Caspase 2 Activation and ER Stress Drive Rapid Jurkat Cell Apoptosis by Clofibrate
Published: Tuesday, September 18, 2012
Author: Fabio Penna et al.

by Fabio Penna, Fabrizio Pin, Domiziana Costamagna, Patrizia Reffo, Francesco Maria Baccino, Gabriella Bonelli, Paola Costelli

Differently from the antiapoptotic action most commonly assigned to peroxisome proliferators (PPs), we demonstrated that some of them, clofibrate (CF) in particular, display clearcut apoptogenic properties on rat hepatoma cell lines. We and others could confirm that CF as well as various other PPs can induce apoptosis in a variety of cells, including human liver, breast and lung cancer cell lines. The present study was aimed at investigating the cytotoxic action of CF on a neoplastic line of different origin, the human T leukemia Jurkat cells. We observed that CF rapidly triggers an extensive and morphologically typical apoptotic process on Jurkat cells, though not in primary T cells, which is completely prevented by the polycaspase inhibitor zVADfmk. Gene silencing studies demonstrated that CF-induced apoptosis in Jurkat cells is partially dependent on activation of caspase 2. Looking for a possible trigger of caspase 2 activation, we observed increased levels of phosphorylated eIF2a and JNK in CF-treated cells. Moreover, intracellular Ca2+ homeostasis was perturbed. Together, these findings are suggestive for the occurrence of ER stress, an event that is known to have the potential to activate caspase 2. The present observations demonstrate that CF induces in Jurkat cells a very fast and extensive apoptosis, that involves induction of ER stress and activation of caspases 2 and 3. Since apoptosis in Jurkat cells occurs at pharmacologically relevant concentrations of CF, the present findings encourage further in depth analysis in order to work out the potential implications of CF cytotoxcity on leukemic cells.