These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Doxorubicin and selenium cooperatively induce fas signaling in the absence of Fas/Fas ligand interaction.
    Author: Li S, Zhou Y, Dong Y, Ip C.
    Journal: Anticancer Res; 2007; 27(5A):3075-82. PubMed ID: 17970047.
    Abstract:
    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.
    [Abstract] [Full Text] [Related] [New Search]