XIAP inhibitor and antiestrogen embelin abrogates metastasis and augments apoptosis in estrogen receptor positive human breast adenocarcinoma cell line MCF-7 K. R. Sumalatha • G. Abiramasundari • G. K. Chetan • T. Divya • G. Sudhandiran • M. Sreepriya Received: 6 January 2013 / Accepted: 20 December 2013 / Published online: 4 January 2014 Ó Springer Science+Business Media Dordrecht 2014 Abstract Tamoxifen therapy for the treatment of hor- mone responsive breast cancer has limitations due to acquired resistance in the case of recurrences. Embelin, a known inhibitor of X-linked inhibitor of apoptosis protein (XIAP) was also reported to exhibit strong antiestrogenic effects in animal models. Dual role of embelin as a proa- poptotic and antiestrogenic agent may have potential ben- efits in the therapy of breast cancer. In this study, the effects of embelin treatment on estrogen receptor positive Human breast adenocarcinoma (MCF-7) cells was inves- tigated to primarily understand if embelin being an anti- estrogen and XIAP inhibitor could be a potential alternative to tamoxifen therapy. Results revealed that, embelin at a concentration of 65 lg/ml attenuated prolif- eration, inhibited metastatic migration, modulated the expression of Bcl2, Caspases and induced apoptosis in MCF-7 cells which was found to be p53 mediated. Hence, chemotherapy with embelin could be a promising strategy to be experimented in hormone responsive breast cancers. Keywords Antiestrogens Á Embelin Á Apoptosis Á XIAP Á MCF-7 Á Breast cancer Introduction Breast cancer is the most common malignancy in women and despite the advances in diagnosis and treatment, it presents the second leading cause of mortality due to cancer in women worldwide [1]. Approximately 70 % of breast cancers are estrogen receptor positive (ER?) and mitogenic estrogen signaling plays a pivotal role in the development and progression of ER? breast cancer [2]. Endocrine therapies, especially treatment with antiestro- gens like tamoxifen is the recommended first line of che- motherapy for ER? breast cancer. Antiestrogens act by competitively binding to estrogen receptors on tumour cells and hence blocking the effects of estrogen [3]. The major setback in the treatment of breast cancer with antiestrogens like tamoxifen is the unresponsiveness to therapy due to acquired resistance or intrinsic insensitivity in case of recurrences. Thus, the search is on for alternative anties- trogenic compounds, which could be employed in the chemotherapy of breast cancer. Dysfunction of the apoptotic machinery is a funda- mental characteristic of cancer that allows the transformed cells to survive and proliferate. In part, this is due to defects in the execution phase of apoptosis. The inhibitor of apoptosis proteins (IAP) are one of the major protein families that regulates Caspase activation and programmed cell death. In particular, one of the IAP proteins, X-linked inhibitor of apoptosis protein (XIAP) has been identified as the most potent Caspase inhibitor to date [4]. XIAP is expressed in almost all tissues and cell types. However, it is often over expressed in tumours versus normal tissue [5, 6]. XIAP is capable of conferring resistance to cancer cells. The benzoquinone and the small molecular inhibitor of XIAP, embelin possess a wide spectrum of biological activities with strong inhibition of NF-KB and down K. R. Sumalatha Á G. Abiramasundari Á M. Sreepriya (&) Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi Campus, Bangalore 560056, Karnataka, India e-mail: mpriya7@yahoo.com G. K. Chetan Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, Karnataka, India T. Divya Á G. Sudhandiran Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600023, Tamil Nadu, India 123 Mol Biol Rep (2014) 41:935–946 DOI 10.1007/s11033-013-2938-z