Breast Cancer Online, 2008, 11(2), Page 1 of 3, e4 doi:10.1017/S1470903108006676 r 2008 Cambridge University Press ISSN 1470-9031 Journals Club Review of: Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells Alison J. Butt 1,2 1 Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; 2 St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Randwick, NSW, Australia Citation of original article: C. Lagadec, E. Adriaenssens, R. A. Toillon, V. Chopin, R. Romon, F. Van Coppenolle, H. Hondermarck, X. Le Bourhis. Oncogene advance online publication, 3 September 2007; doi:10.1038/sj.onc.1210749. Abstract of the original article: Tamoxifen (TAM), is widely used as a single agent in adjuvant treatment of breast cancer. Here, we invest- igated the effects of TAM in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in estrogen receptor-a (ER-a)-positive and -negative breast cancer cells. We showed that cotreatment with TAM and TRAIL synergistically induced apoptosis regardless of ER-a status. By contrast, cotreatment did not affect the viability of normal breast epithelial cells. Cotreatment with TAM and TRAIL in breast cancer cells decreased the levels of antiapoptotic proteins including FLIPs and Bcl-2, and enhanced the levels of pro- apoptotic proteins such as FADD, caspase 8, tBid, Bax and caspase 9. Furthermore, cotreatment-induced apoptosis was efficiently reduced by FADD- or Bid-siRNA, indicating the implication of both extrinsic and intrinsic pathways in synergistic apoptosis induction. Importantly, cotreatment totally arrested tumor growth in an ER-a-negative MDA-MB-231 tumor xenograft model. The abrogation of tumor growth correlated with enhanced apoptosis in tumor tissues. Our findings raise the possibility to use TAM in combination with TRAIL for breast cancers, regardless of ER-a status. Review Breast cancer remains a leading cause of female mortality in the Western world. Despite the significant clinical effectiveness of antioestrogen therapies such as tamoxifen (TAM) for patients with oestrogen receptor (ER)-positive disease, therapeutic respon- siveness is often short-lived and compromised by the development of resistance [1,2]. Thus, the clinical need for novel therapeutic approaches with increased efficacy has provided the rationale for exploring the interactions between endocrine and non-endocrine therapies as a means of enhancing and broadening responsiveness and overcoming resistance. As the intricacies of mammalian cell death signal- ling become further elucidated, the possibility of manipulating the intracellular apoptotic machinery for therapeutic benefit is being explored experimentally [3]. Promising candidates from this approach include BH3 mimetics that act by neutralising pro-survival Bcl-2 proteins [4], and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL is a member Correspondence to: Alison J. Butt, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. E-mail: a.butt@ garvan.org.au Received: 22/01/08 Accepted: 23/01/08 BCO/667/2007/JC https://www.cambridge.org/core/terms. https://doi.org/10.1017/S1470903108006676 Downloaded from https://www.cambridge.org/core. IP address: 18.215.181.253, on 26 Nov 2021 at 12:34:25, subject to the Cambridge Core terms of use, available at