ArticleOncology letters2020
Genipin enhances the antitumor effect of elesclomol in A549 lung cancer cells by blocking uncoupling protein-2 and stimulating reactive oxygen species production.
Article in Oncology letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.Frontiers in oncology · 2025Pooled it
- Acylcarnitines in Cancer Metabolism: Mechanistic Insights and Stratification Potential.Cancers · 2026Review
- Mito-Genipin, a Novel Mitochondria-Targeted Genipin Derivative Modulates Oxidative Stress and Inflammation in Macrophages.Antioxidants (Basel, Switzerland) · 2025Article
- Engineering Inorganic Nanoparticles to Induce Cuproptosis: A New Strategy for Cancer Therapy.Pharmaceutics · 2025Review
- Cuproptosis: a novel therapeutic mechanism in lung cancer.Cancer cell international · 2025Review
- An up-To-Date Review of Elesclomol and Its Nano-Formulations in Cancer Therapy.Cancer reports (Hoboken, N.J.) · 2025Review
- Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity.Journal of translational internal medicine · 2025Article
- Genipin-Simple but Significant Bioactive Iridoid for Therapeutical Application and Beyond: A Review.Life (Basel, Switzerland) · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives.International journal of molecular sciences · 2024Review
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Cuproptosis in cancer: biological implications and therapeutic opportunities.Cellular & molecular biology letters · 2024Review
- Cuproptosis in lung cancer: mechanisms and therapeutic potential.Molecular and cellular biochemistry · 2024Review
- UCP2 promotes NSCLC proliferation and glycolysis via the mTOR/HIF-1α signaling.Cancer medicine · 2024Article
- Elesclomol, a copper-transporting therapeutic agent targeting mitochondria: from discovery to its novel applications.Journal of translational medicine · 2023Review
- Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway.World journal of diabetes · 2023Article
- Role of UCP2 in the Energy Metabolism of the Cancer Cell Line A549.International journal of molecular sciences · 2023Article
- Association between Polymorphism of GenesGenes · 2023Article
- Copper in cancer: from limiting nutrient to therapeutic target.Frontiers in oncology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The uncoupling protein-2 (UCP2) serves a role in tumor aggressiveness and anticancer resistance, which is considered to be associated with its ability to attenuate reactive oxygen species (ROS) production. We hypothesized that UCP2 may protect cancer cells from elesclomol-induced cytotoxicity, and that this may be overcome by blocking UCP2 function with genipin. In A549 lung cancer cells that exhibited high UCP2 expression, treatment with elesclomol alone induced limited changes in glucose uptake, ROS production and cell survival. By contrast, both UCP2 knockdown and genipin treatment mildly reduced glucose uptake, increased ROS production and decreased cell survival. Combining genipin and elesclomol further reduced glucose uptake and increased cellular and mitochondrial ROS production. Moreover, co-treatment with genipin and elesclomol reduced the colony forming capacity to 50.6±7.4% and the cell survival to 42.0±3.4% of that in the control cells (both P<0.001). Suppression of cell survival by treatment with elesclomol and genipin was enhanced in the presence of an exogenous ROS inducer and attenuated by a ROS scavenger. The cytotoxic effects of combining genipin and elesclomol were accompanied by reduced mitochondrial membrane potential and occurred through apoptosis as demonstrated by Annexin V assay and increased protein cleavage of PARP and caspase-3. Finally, in an A549 ×enograft mouse model, tumor growth was only modestly retarded by treatment with elesclomol or genipin alone, but was markedly suppressed by combining the two drugs compared with that in the control group (P=0.008). Therefore, high UCP2 expression may limit the antitumor effect of elesclomol by attenuating ROS responses, and this may be overcome by co-treatment with genipin; combining elesclomol and genipin may be an effective strategy for treating cancers with high UCP2.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.