The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells

Derdak, Z; Mark, N.M.; Beldi, G; Robson, S.C.; Wands, J.R.; Baffy, G (2008). The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer research, 68(8), pp. 2813-9. Birmingham, Ala.: American Association for Cancer Research AACR 10.1158/0008-5472.CAN-08-0053

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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 NH(2)-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Beldi, Guido

ISSN:

0008-5472

ISBN:

1538-7445 (Electroni

Publisher:

American Association for Cancer Research AACR

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:04

Last Modified:

10 Nov 2014 07:40

Publisher DOI:

10.1158/0008-5472.CAN-08-0053

Web of Science ID:

000255100500033

URI:

https://boris.unibe.ch/id/eprint/27696 (FactScience: 110169)

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