Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma
Article first published online: 11 APR 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
British Journal of Haematology
Volume 141, Issue 5, pages 659–671, June 2008
How to Cite
Okawa, Y., Hideshima, T., Ikeda, H., Raje, N., Vallet, S., Kiziltepe, T., Yasui, H., Enatsu, S., Pozzi, S., Breitkreutz, I., Cirstea, D., Santo, L., Richardson, P. and Anderson, K. C. (2008), Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma. British Journal of Haematology, 141: 659–671. doi: 10.1111/j.1365-2141.2008.07114.x
- Issue published online: 15 APR 2008
- Article first published online: 11 APR 2008
- Received 30 October 2007; accepted for publication 7 January 2008
- multiple myeloma;
- fatty acid synthase;
Okawa, Y., Hideshima, T., Ikeda, H., Raje, N., Vallet, S., Kiziltepe,T., Yasui, H., Enatsu, S., Pozzi, S., Breitkreutz, I., Cirstea, D., Santo, L.,Richardson, P. & Anderson, K.C. (2008) Fatty acid synthase is a novel therapeutic target in multiple myeloma. British Journal of Haematology, 141, 659–671.
The above article, published in the online issue, 141·5 on 7 May 2008 in Blackwell Synergy (http://www.blackwell-synergy.com), has been retracted by agreement between the authors, the Journal Editor-in-Chief and Blackwell Publishing Ltd.
British Journal of Haematology
This study investigated the biological significance of the inhibition of fatty acid synthase (FAS) in multiple myeloma (MM) using the small molecule inhibitor Cerulenin. Cerulenin triggered growth inhibition in both MM cell lines and MM patient cells, and overcame the survival and growth advantages conferred by interleukin-6, insulin-like growth factor-1, and bone marrow stromal cells. It induced apoptosis in MM cell lines with only modest activation of caspase -8, -9, -3 and PARP; moreover, the pan-caspase inhibitor Z-VAD-FMK did not inhibit Cerulenin-induced apoptosis and cell death. In addition, treatment of MM cells with Cerulenin primarily up-regulated apoptosis-inducing factor/endonuclease G, mediators of caspase-independent apoptosis. Importantly, Cerulenin induced endoplasmic reticulum stress response via up-regulation of the Grp78/IRE1α/JNK pathway. Although the C-Jun-NH2-terminal kinase (JNK) inhibitor SP600215 blocked Cerulenin-induced cytotoxicity, it did not inhibit apoptosis and caspase cleavage. Furthermore, Cerulenin showed synergistic cytotoxic effects with various agents including Bortezomib, Melphalan and Doxorubicin. Our results therefore indicate that inhibition of FAS by Cerulenin primarily triggered caspase-independent apoptosis and JNK-dependent cytotoxicity in MM cells. This report demonstrated that inhibition of FAS has anti-tumour activity against MM cells, suggesting that it represents a novel therapeutic target in MM.