resveratrol reduced survivin expression

Discussion in 'Health and medical' started by Roger, Feb 23, 2004.

  1. Roger

    Roger Guest

    Cancer Res. 2004 Jan 1;64(1):337-46.

    Sensitization for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by the
    chemopreventive agent resveratrol.

    Fulda S, Debatin KM. University Children's Hospital, Ulm, Germany.

    Survivin is a member of the inhibitor of apoptosis proteins that is expressed at high levels in most
    human cancers and may facilitate evasion from apoptosis and aberrant mitotic progression. Naturally
    occurring dietary compounds such as resveratrol have gained considerable attention as cancer
    chemopreventive agents. Here, we discovered a novel function of the chemopreventive agent
    resveratrol: resveratrol is a potent sensitizer of tumor cells for tumor necrosis factor-related apoptosis-
    inducing ligand (TRAIL)-induced apoptosis through p53-independent induction of p21 and p21-mediated
    cell cycle arrest associated with survivin depletion. Concomitant analysis of cell cycle, survivin
    expression, and apoptosis revealed that -induced G(1) arrest was associated with down-regulation of
    survivin expression and sensitization for TRAIL-induced apoptosis. Accordingly, G(1) arrest using
    the cell cycle inhibitor mimosine or induced by p21 overexpression reduced survivin expression and
    sensitized cells for TRAIL treatment. Likewise, resveratrol-mediated cell cycle arrest followed by
    survivin depletion and sensitization for TRAIL was impaired in p21- deficient cells. Also, down-
    regulation of survivin using survivin antisense oligonucleotides sensitized cells for TRAIL-induced
    apoptosis. Importantly, resveratrol sensitized various tumor cell lines, but not normal human
    fibroblasts, for apoptosis induced by death receptor ligation or anticancer drugs. Thus, this
    combined sensitizer (resveratrol)/inducer (e.g., TRAIL) strategy may be a novel approach to enhance
    the efficacy of TRAIL-based therapies in a variety of human cancers.