RT Journal Article
SR Electronic
T1 Doxorubicin and Selenium Cooperatively Induce Fas Signaling in the Absence of Fas/Fas Ligand Interaction
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3075
OP 3082
VO 27
IS 5A
A1 LI, SONG
A1 ZHOU, YUNFEI
A1 DONG, YAN
A1 IP, CLEMENT
YR 2007
UL http://ar.iiarjournals.org/content/27/5A/3075.abstract
AB Background: The synergistic effect of doxorubicin and selenium in apoptosis induction in MCF-7 breast cancer cells has been previously reported. Mitochondrial activation of caspase-9 is in part responsible for the synergy. The present study aimed at examining the death receptor pathway in activating caspase-8 by the two-drug combination. Materials and Methods: We determined the expression of TRAIL and FasL signaling molecules and monitored activated caspase-8 in response to neutralizing/blocking antibodies against ligands/receptors. Results: Our data suggest that TRAIL signaling might not play a role. With respect to the Fas pathway, it was found that doxorubicin enhanced Fas oligomerization (i.e. activation) independent of FasL-Fas interaction. Selenium, on the other hand, increased the expression of FADD, a key adaptor molecule responsible for recruitment of caspase-8 to the Fas oligomer. The significance of the above changes was confirmed by the detection of considerably more caspase-8 in both the Fas or FADD immunoprecipitate obtained from cells treated with the doxorubicin/selenium combination. Conclusion: Doxorubicin and selenium cooperatively activate Fas signaling by targeting key regulatory steps. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved