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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells
Cancer Research, Volume 68, No. 8, Year 2008
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Description
Cancer cells acquire drug resistance as a result of selection pressure dictated by unfavorable microenvironments. This survival process is facilitated through efficient control of oxidative stress originating from mitochondria that typically initiates programmed cell death. We show this critical adaptive response in cancer cells to be linked to uncoupling protein-2 (UCP2), a mitochondrial suppressor of reactive oxygen species (ROS). UCP2 is present in drug-resistant lines of various cancer cells and in human colon cancer. Overexpression of UCP2 in HCT116 human colon cancer cells inhibits ROS accumulation and apoptosis after exposure to chemotherapeutic agents. Tumor xenografts of UCP2-overexpressing HCT116 cells retain growth in nude mice receiving chemotherapy. Augmented cancer cell survival is accompanied by altered NH2-terminal phosphorylation of the pivotal tumor suppressor p53 and induction of the glycolytic phenotype (Warburg effect). These findings link UCP2 with molecular mechanisms of chemoresistance. Targeting UCP2 may be considered a novel treatment strategy for cancer. ©2008 American Association for Cancer Research.
Authors & Co-Authors
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Wands, Jack R.
United States, Providence
Liver Research Center
Baffy, György
United States, Providence
Liver Research Center
United States, Boston
Brigham and Women's Hospital
Statistics
Citations: 228
Authors: 3
Affiliations: 3
Identifiers
Doi:
10.1158/0008-5472.CAN-08-0053
ISSN:
00085472
Research Areas
Cancer