alexa Chemotherapeutic drug-induced apoptosis in human leukaemic cells is independent of the Fas (APO-1 CD95) receptor ligand system.
Haematology

Haematology

Journal of Blood Disorders & Transfusion

Author(s): McGahon AJ, Costa Pereira AP, Daly L, Cotter TG, McGahon AJ, Costa Pereira AP, Daly L, Cotter TG

Abstract Share this page

Abstract The potential role of the Fas (CD95/APO-1) receptor/ligand system in chemotherapeutic drug-induced apoptosis was examined in a number of human leukaemic cell lines. Flow cytometric profiles of doxorubicin-treated HL-60, K562, U937 and Jurkat cells failed to show any significant increase in Fas or Fas ligand expression over 24 h, despite the induction of significant levels of apoptosis in these cells. Although preincubation of human leukaemic cells with a neutralizing anti-Fas IgG antibody blocked anti-Fas IgM-induced apoptosis, this strategy failed to inhibit chemotherapeutic drug-induced apoptosis. To determine whether recruitment of the Fas/Fas ligand complex during drug-induced apoptosis was a cell-specific event we utilized the CEM cell line. Doxorubicin treatment of CEM cells over 24 h failed to show any up-regulation in Fas or Fas ligand protein levels as detected by flow cytometry. Furthermore, neutralizing anti-Fas IgG Ab failed to inhibit chemotherapeutic drug-induced apoptosis in CEM cells. The present studies do, however, demonstrate a role for anti-Fas IgM Ab in producing a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs. Low-dose anti-Fas IgM treatment in combination with doxorubicin, methotrexate, camptothecin and etoposide produced an augmented cytoxicity in CEM cells. Taken together these observations demonstrate that although recruitment of the Fas/APO-1/CD95 receptor/ligand system is not a necessary requirement for chemotherapeutic drug-induced apoptosis, combination of anti-Fas IgM and drug treatment produces a synergistic cytotoxic effect which may prove useful in the treatment of human leukaemias.
This article was published in Br J Haematol and referenced in Journal of Blood Disorders & Transfusion

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords