Doxorubicin and selenium cooperatively induce fas signaling in the absence of Fas/Fas ligand interaction.
Doxorubicin and selenium cooperatively induce fas signaling in the absence of Fas/Fas ligand interaction.
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发表时间：
2007-09
影响因子：
2
通讯作者：
Song Li;Yunfei Zhou;Yan Dong;C. Ip
中科院分区：
文献类型：
--
作者：
Song Li;Yunfei Zhou;Yan Dong;C. Ip
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.
