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Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Author

Listed:
  • Lakshmi Raj

    (Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School)

  • Takao Ide

    (Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School)

  • Aditi U. Gurkar

    (Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School)

  • Michael Foley

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Monica Schenone

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Xiaoyu Li

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Nicola J. Tolliday

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Todd R. Golub

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Steven A. Carr

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Alykhan F. Shamji

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Andrew M. Stern

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Anna Mandinova

    (Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School
    Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Stuart L. Schreiber

    (Broad Institute of Harvard and MIT, 7 Cambridge Center)

  • Sam W. Lee

    (Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School
    Broad Institute of Harvard and MIT, 7 Cambridge Center)

Abstract

ROS-mediated anticancer compound A chemical screen has identified a small molecule, piperlongumine (PL), as a compound that induces selective killing of cancer cells. Piperlongumine acts by increasing reactive oxygen species (ROS) levels in cancer cells. Although it is active against a number of tumour models in vivo irrespective of p53 status, it does not affect normal tissues, including rapidly proliferating non-tumour cells. This work suggests a novel strategy for eradicating cancer cells by targeting the ROS stress-response pathway, but further work will be needed to identify determinants of piperlongumine sensitivity in a wider range of cancers.

Suggested Citation

  • Lakshmi Raj & Takao Ide & Aditi U. Gurkar & Michael Foley & Monica Schenone & Xiaoyu Li & Nicola J. Tolliday & Todd R. Golub & Steven A. Carr & Alykhan F. Shamji & Andrew M. Stern & Anna Mandinova & S, 2011. "Selective killing of cancer cells by a small molecule targeting the stress response to ROS," Nature, Nature, vol. 475(7355), pages 231-234, July.
    • Handle: RePEc:nat:nature:v:475:y:2011:i:7355:d:10.1038_nature10167
    DOI: 10.1038/nature10167
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