TRAIL Sensitization of PC3 Prostate Cancer Cells by Doxorubicin Can Be Blocked by the Antioxidant N-Acetyl-Cysteine or by the Iron Chelator Deferoxamine

    October 2006 in “ Clinical Cancer Research ”
    Shai J. White, Laura M. Kasman, Laura Spruill, Paul J. McDermott, Christina Voelkel‐Johnson
    TLDR Antioxidants can block the cancer-fighting effects of doxorubicin.
    The study investigated how doxorubicin sensitized PC3 prostate cancer cells to TRAIL by downregulating the anti-apoptotic protein FLIPs through translational inhibition, specifically via EF2 phosphorylation caused by oxidative stress. This effect was blocked by the antioxidant N-Acetyl-Cysteine (NAC) or the iron chelator deferoxamine (DFO), which prevented FLIPs downregulation and EF2 phosphorylation, but did not affect doxorubicin-induced G2 cell-cycle arrest. The findings suggested that antioxidants might protect tumors from doxorubicin's effectiveness, highlighting the need for personalized treatment strategies based on tumor protein profiling.
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