ArticleCell death & disease2017
Critical role of reactive oxygen species (ROS) for synergistic enhancement of apoptosis by vemurafenib and the potassium channel inhibitor TRAM-34 in melanoma cells.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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
42 citing papers in PubMed, 66 citations in OpenAlex.
- Potassium channels in cancer: from hallmarks to therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- Exploiting metabolic adaptations to overcome dabrafenib treatment resistance in melanoma cells.Molecular oncology · 2026Article
- Article
- Investigating the Role of Peroxisomes in Regulating Breast Cancer Stem Cell Mechanisms.International journal of molecular sciences · 2025Article
- The cell cycle regulator PLK1 promotes murine melanoma progression by regulating the transcription factor BACH1.PLoS biology · 2025Article
- TPP-Based Nanovesicles Kill MDR Neuroblastoma Cells and Induce Moderate ROS Increase, While Exerting Low Toxicity Towards Primary Cell Cultures: An In Vitro Study.International journal of molecular sciences · 2025Article
- Review
- Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring BRAFHistology and histopathology · 2024Article
- Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xInternational journal of molecular sciences · 2024Article
- Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells.International journal of molecular sciences · 2023Review
- Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins.International journal of molecular sciences · 2023Article
- A potent ion channel blocker, hydroquinidine, exhibits strong anti-cancer activity on colon, pancreatic, and hepatocellular cancer cells.Molecular biology reports · 2023Article
- A Meroterpenoid from Tibetan Medicine Induces Lung Cancer Cells Apoptosis through ROS-Mediated Inactivation of the AKT Pathway.Molecules (Basel, Switzerland) · 2023Article
- Functional expression of mitochondrial KPflugers Archiv : European journal of physiology · 2022Article
- Article
- Pharmacological modulation of Kv1.3 potassium channel selectively triggers pathological B lymphocyte apoptosis in vivo in a genetic CLL model.Journal of experimental & clinical cancer research : CR · 2022Article
- Ion Channel Involvement in Tumor Drug Resistance.Journal of personalized medicine · 2022Review
- Stress Responses as Master Keys to Epigenomic Changes in Transcriptome and Metabolome for Cancer Etiology and Therapeutics.Molecular and cellular biology · 2022Article
- KScientific reports · 2021Article
- Autophagy Inhibition in BRAF-Driven Cancers.Cancers · 2021Review
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
Inhibition of MAP kinase pathways by selective BRAF inhibitors, such as vemurafenib and dabrafenib, have evolved as key therapies of BRAF-mutated melanoma. However, tumor relapse and therapy resistance have remained as major problems, which may be addressed by combination with other pathway inhibitors. Here we identified the potassium channel inhibitor TRAM-34 as highly effective in combination with vemurafenib. Thus apoptosis was significantly enhanced and cell viability was decreased. The combination vemurafenib/TRAM-34 was also effective in vemurafenib-resistant cells, suggesting that acquired resistance may be overcome. Vemurafenib decreased ERK phosphorylation, suppressed antiapoptotic Mcl-1 and enhanced proapoptotic Puma and Bim. The combination resulted in enhancement of proapoptotic pathways as caspase-3 and loss of mitochondrial membrane potential. Indicating a special mechanism of vemurafenib-induced apoptosis, we found strong enhancement of intracellular ROS levels already at 1 h of treatment. The critical role of ROS was demonstrated by the antioxidant vitamin E (α-tocopherol), which decreased intracellular ROS as well as apoptosis. Also caspase activation and loss of mitochondrial membrane potential were suppressed, proving ROS as an upstream effect. Thus ROS represents an initial and independent apoptosis pathway in melanoma cells that is of particular importance for vemurafenib and its combination with TRAM-34.
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.