• Open Access

Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma

Authors

  • Yutaka Okawa,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    2. Division of Oncology and Haematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
    Search for more papers by this author
  • Teru Hideshima,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Hiroshi Ikeda,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Noopur Raje,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Sonia Vallet,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Tanyel Kiziltepe,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Hiroshi Yasui,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Sotaro Enatsu,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Samantha Pozzi,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Iris Breitkreutz,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Diana Cirstea,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Loredana Santo,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Paul Richardson,

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author
  • Kenneth C. Anderson

    1. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Search for more papers by this author

  • Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

Kenneth C. Anderson, MD, Dana-Farber Cancer Institute, Mayer 557, 44 Binney Street, Boston, MA 02115, USA. E-mail: kenneth_anderson@dfci.harvard.edu and Yutaka Okawa, MD, PhD, Dana-Farber Cancer Institute, Mayer 549, 44 Binney Street, Boston, MA 02115, USA. E-mail: yutaka_okawa@dfci.harvard.edu

Abstract

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.

Finbarr Cotter

Editor-in-Chief

British Journal of Haematology

Summary

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.

Ancillary