ArticleInternational journal of molecular sciences2019
The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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
12 citing papers in PubMed, 43 citations in OpenAlex.
- Novel copper-phenothiazine-amino acid complexes exhibit selective anticancer activity via induction of apoptosis and cell cycle arrest in HepG2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- The Managed Acquisition of Chemoresistance as an Informative Tool for Tumor Research.International journal of molecular sciences · 2025Review
- Statins regulate kinase signaling by causing changes in phosphorylation, rather than through changes in gene expression or direct inhibition: evidence in colorectal cancer.Frontiers in pharmacology · 2025Article
- Article
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Repurposing Antidepressants and Phenothiazine Antipsychotics as Efflux Pump Inhibitors in Cancer and Infectious Diseases.Antibiotics (Basel, Switzerland) · 2023Review
- KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.Journal of experimental & clinical cancer research : CR · 2023Article
- Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells.Frontiers in oncology · 2023Review
- Antipsychotic Drug Fluphenazine against Human Cancer Cells.Biomolecules · 2022Review
- Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Therapeutic Mechanisms of Phenothiazine Drugs: A Mini-Review of Advances in Cancer Treatment and Antibiotic Resistance.Iranian journal of pharmaceutical research : IJPRReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Since none of the multidrug resistance (MDR) modulators tested so far found their way into clinic, a novel approach to overcome the MDR of cancer cells has been proposed. The combined use of two MDR modulators of dissimilar mechanisms of action was suggested to benefit from the synergy between them. The effect of three phenothiazine derivatives that were used as single agents and in combination with simvastatin on cell growth, apoptosis induction, activity, and expression of cyclooxygenase-2 (COX-2) in doxorubicin-resistant colon cancer cells (LoVo/Dx) was investigated. Treatment of LoVo/Dx cells by phenothiazine derivatives combined with simvastatin resulted in an increase of doxorubicin cytotoxicity and its intracellular accumulation as compared to the treatment with phenothiazine derivatives that were used as single agents. Similarly, LoVo/Dx cells treated with two-component mixture of modulators showed the reduced expression of ABCB1 (P-glycoprotein) transporter and COX-2 enzyme, both on mRNA and protein level. Reduced expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax were also detected. Additionally, COX-2 activity was diminished, and caspase-3 activity was increased to a higher extent by phenothiazine derivative:simvastatin mixtures than by phenothiazine derivatives themselves. Therefore, the introduction of simvastatin strengthened the anti-MDR, anti-inflammatory, and pro-apoptotic properties of phenothiazines in LoVo/Dx cells.
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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.