ArticleOncotarget2015
Calmodulin antagonists promote TRA-8 therapy of resistant pancreatic cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- Calcium and Non-Penetrating Traumatic Brain Injury: A Proposal for the Implementation of an Early Therapeutic Treatment for Initial Head Insults.Biomolecules · 2024Review
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- CaBiomolecules · 2023Review
- Protein Biomarkers Shared by Multiple Neurodegenerative Diseases Are Calmodulin-Binding Proteins Offering Novel and Potentially Universal Therapeutic Targets.Journal of clinical medicine · 2023Review
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- Understanding the role of dopamine in cancer: past, present and future.Carcinogenesis · 2022Review
- Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Calmodulin binding proteins and neuroinflammation in multiple neurodegenerative diseases.BMC neuroscience · 2022Review
- Calmodulin Binding Proteins and Alzheimer's Disease: Biomarkers, Regulatory Enzymes and Receptors That Are Regulated by Calmodulin.International journal of molecular sciences · 2020Review
- Regulation of pancreatic cancer TRAIL resistance by protein O-GlcNAcylation.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Antipsychotic Drug Trifluoperazine Suppresses Colorectal Cancer by Inducing G0/G1 Arrest and Apoptosis.Frontiers in pharmacology · 2019Article
- Trifluoperazine prevents FOXO1 nuclear excretion and reverses doxorubicin-resistance in the SHG44/DOX drug-resistant glioma cell line.International journal of molecular medicine · 2018Article
- Calmodulin antagonist enhances DR5-mediated apoptotic signaling in TRA-8 resistant triple negative breast cancer cells.Journal of cellular biochemistry · 2018Article
- Assessment of Three-Drug Combination Pharmacodynamic Interactions in Pancreatic Cancer Cells.The AAPS journal · 2018Article
- Low concentration trifluoperazine promotes proliferation and reduces calcium-dependent apoptosis in glioma cells.Scientific reports · 2018Article
- Identification of CALM as the potential serum biomarker for predicting the recurrence of nasopharyngeal carcinoma using a mass spectrometry-based comparative proteomic approach.International journal of molecular medicine · 2017Article
- Calmodulin Binding to Death Receptor 5-mediated Death-Inducing Signaling Complex in Breast Cancer Cells.Journal of cellular biochemistry · 2017Article
- The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand.The Journal of biological chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic cancer is highly malignant with limited therapy and a poor prognosis. TRAIL-activating therapy has been promising, however, clinical trials have shown resistance and limited responses of pancreatic cancers. We investigated the effects of calmodulin(CaM) antagonists, trifluoperazine(TFP) and tamoxifen(TMX), on TRA-8-induced apoptosis and tumorigenesis of TRA-8-resistant pancreatic cancer cells, and underlying mechanisms. TFP or TMX alone did not induce apoptosis of resistant PANC-1 cells, while they dose-dependently enhanced TRA-8-induced apoptosis. TMX treatment enhanced efficacy of TRA-8 therapy on tumorigenesis in vivo. Analysis of TRA-8-induced death-inducing-signaling-complex (DISC) identified recruitment of survival signals, CaM/Src, into DR5-associated DISC, which was inhibited by TMX/TFP. In contrast, TMX/TFP increased TRA-8-induced DISC recruitment/activation of caspase-8. Consistently, caspase-8 inhibition blocked the effects of TFP/TMX on TRA-8-induced apoptosis. Moreover, TFP/TMX induced DR5 expression. With a series of deletion/point mutants, we identified CaM antagonist-responsive region in the putative Sp1-binding domain between -295 to -300 base pairs of DR5 gene. Altogether, we have demonstrated that CaM antagonists enhance TRA-8-induced apoptosis of TRA-8-resistant pancreatic cancer cells by increasing DR5 expression and enhancing recruitment of apoptotic signal while decreasing survival signals in DR5-associated DISC. Our studies support the use of these readily available CaM antagonists combined with TRAIL-activating agents for pancreatic cancer therapy.
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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.