Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 54
Synergistic apoptosis induction of breast cancer cells by tamoxifen and TRAIL
Lagadec C, Chopin V, Anderiaenssens E, Hondermarck H, Le Bourhis X
ERI-8 INSERM "Signalisation des facteurs de croissance dans le cancer du sein.
Proteomique fonctionnelle" UPRES-EA 1033, IFR-118 Université des Sciences et
Technologies de Lille, France
Although tamoxifen is widely used in the treatment of breast cancer expressing ostrogen
receptors (ER); it has been recently reported that tamoxifen can induce apoptosis of ERnegative
breast cancer cells. On the other hand, the TNF-related apoptosis-inducing ligand
(TRAIL), also called Apo2L, has been the subject of recent research as a potential new
anticancer agent. We investigated the effect of tamoxifen alone or in combination with
TRAIL in breast cancer cells. We showed that TRAIL-induced apoptosis was potentiated by
tamoxifen in both ER-positive and ER-negative breast cancer cells. From a mechanistic
standpoint, combination treatment with tamoxifen and TRAIL resulted in increased cleavage
of procasepases-8, 9 and Bid. Tamoxifen and TRAIL cooperated also to increase the
expression of FADD, procaspase-8, Bax and Bid and to decrease the expression of FLIP and
Bcl-2. These modifications could constitute multiple amplification loops to result from the
final synergistic induction of apoptosis. Importantly, the combination treatment with
tamoxifen and TRAIL did not affect the viability of cultured normal breast epithelial cells.
Moreover, tamoxifen and TRAIL were well tolerated in mice and the combination of
tamoxifen and TRAIL dramatically reduced tumor burden in in vivo MDA-MB-231 tumor
xenograf model. These data suggest that combination of tamoxifen and TRAIL may be useful
in the treatment of ER negative breast cancers.
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