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RETRACTED ARTICLE: Late phase activation of nuclear transcription factor kappaB by doxorubicin is mediated by interleukin-8 and induction of apoptosis via FasL

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

This article was retracted on 24 March 2013

An Erratum to this article was published on 21 October 2012

Abstract

Doxorubicin is one of the most effective molecules used in the treatment of various tumors. Contradictory reports often open windows to understand the doxorubicin-mediated signaling to exert its apoptosis effect. In this report, we provide evidences that doxorubicin induced biphasic induction of nuclear factor kappaB (NF-κB) of immediate activation followed by decrease in the amount of RelA (p65) subunit possibly by inducing the activity of proteasome, but not proteases. Further induction of NF-κB was observed through interleukin 8 (IL-8), expressed by doxorubicin treatment. Increased amount of IL-8 induced apoptosis via increase in the releases of intracellular Ca2+, activation of calcineurin, nuclear translocation of nuclear factor activated T cell (NF-AT), and NF-AT-dependent FasL expression. Anti-IL-8 or -FasL antibody, dominant negative TRAF6 (TRAF6-DN), or TRAF6 binding peptide (TRAF6-BP) inhibited doxorubicin-mediated late phase induction of NF-κB and diminished cell death. Thus, our study clearly demonstrated that doxorubicin-mediated cell death is obtained through expression of IL-8. IL-8-mediated calcification is required for enhancement of doxorubicin-mediated cell death. Overall, this study will help to understand the much studied chemotherapeutic drug, doxorubicin-mediated cell signaling cascade to exert its effect during chemotherapy.

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Acknowledgments

This work was supported by the core grant of Centre for DNA Fingerprinting and Diagnostics (CDFD). We acknowledge the Department of Science and Technology (DST) for providing SEARC Fast Track proposal for Young Scientists grant to SKM and Council for Scientific & Industrial Research (CSIR), New Delhi for providing fellowship to CG and MT. We thank Drs. T. Ramasarma and A. K. Khar for critically and carefully reading the manuscript.

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Authors and Affiliations

  1. Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad, 500001, India

    Charitha Gangadharan, Maikho Thoh & Sunil Kumar Manna

Authors
  1. Charitha Gangadharan
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  2. Maikho Thoh
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  3. Sunil Kumar Manna
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Corresponding author

Correspondence to Sunil Kumar Manna.

Additional information

This article has been retracted at the request of the Centre for DNA Fingerprinting and Diagnostics as it contains manipulated figures.

The retraction note to this article can be found online at http://dx.doi.org/10.1007/s10549-013-2482-5.

An erratum to this article can be found online at http://dx.doi.org/10.1007/s10549-012-2293-0.

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Gangadharan, C., Thoh, M. & Manna, S.K. RETRACTED ARTICLE: Late phase activation of nuclear transcription factor kappaB by doxorubicin is mediated by interleukin-8 and induction of apoptosis via FasL. Breast Cancer Res Treat 120, 671–683 (2010). https://doi.org/10.1007/s10549-009-0493-z

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  • DOI: https://doi.org/10.1007/s10549-009-0493-z

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