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

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 (), Stuart L. Schreiber () and Sam W. Lee ()
Additional contact information
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
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

Nature, 2011, vol. 475, issue 7355, 231-234

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.

Date: 2011
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DOI: 10.1038/nature10167

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