The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Low concentrations (1-5 μM) of FCCP promote cancer cell survival in response to topoisomerase inhibitors or gemcitabine, reducing apoptosis triggered by these molecules.
“Low concentrations (1–5 μM) of FCCP also promote cancer cell survival in response to topoisomerase inhibitors [178] or other chemotherapeutic agents, such as gemcitabine [179], reducing apoptosis triggered by these molecules.”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [178]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 32 · Cited by 229
- Authors
- Derdak, Z., Mark, N. M., Beldi, G., Robson, S. C., Wands, J. R., & Baffy, G.
- Affiliations
- 1Division of Gastroenterology and Liver Research Center, Brown Medical School and Rhode Island Hospital, Providence, Rhode Island and
- Brown University (US)
- Beth Israel Deaconess Medical Center (US)
- Venue
- Cancer Research
- Published
- 2008-04-15
- Volume
- 68
- Issue
- 8
- Pages
- 2813-2819
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2386271
- OpenAlex
- W2111889825
- Cited by
- 229
- References
- 32
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 11 · 2022: 14 · 2021: 14 · 2020: 11 · 2019: 18 · 2018: 13 · 2017: 16 · 2016: 14 · 2015: 14 · 2014: 14 · 2013: 14 · 2012: 16
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL094400)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 61890, K08DK061890)
- National Center for Research Resources (P20RR017695, RR-17695)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- UCP2, chemoresistance, reactive oxygen species, oxidative stress, apoptosis, colon cancer, HCT116 cells, p53 phosphorylation, Warburg effect, glycolysis, tumor xenografts, mitochondrial reactive oxygen species
- MeSH terms
- Uncoupling Protein 2, Animals, Antineoplastic Agents, Cell Division, Colonic Neoplasms, Glycolysis, Humans, Ion Channels, Mice, Nude, Mitochondria, Transplantation, Heterologous, Ultraviolet Rays, Gene Expression Regulation, Neoplastic, Polymerase Chain Reaction, Tumor Suppressor Protein p53, Apoptosis, Reactive Oxygen Species, Drug Resistance, Neoplasm, Mitochondrial Proteins, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
