ArticleArchivum immunologiae et therapiae experimentalis2021
Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition.
Article in Archivum immunologiae et therapiae experimentalis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 38 citations in OpenAlex.
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- Deactivation of CK1α enhances the anti-cancer effects of salinomycin in colorectal cancer HCT116 cells.Biochemistry and biophysics reports · 2025Article
- Hesperetin reduces neuronal death in an SHSY5Y Alzheimer's model by inhibiting inflammation and apoptosis and pyroptosis cell death pathways.Scientific reports · 2025Article
- Deciphering the roles of non-coding RNAs in liposarcoma development: Challenges and opportunities for translational therapeutic advances.Non-coding RNA research · 2025Review
- Effect of 30-day Ramadan fasting on autophagy pathway and metabolic health outcome in healthy individuals.Molecular biology research communications · 2025Article
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- Tumour-specific phosphorylation of serine 419 drives alpha-enolase (ENO1) nuclear export in triple negative breast cancer progression.Cell & bioscience · 2024Article
- Melittin as an Activator of the Autophagy and Unfolded Protein Response Pathways in Colorectal HCT116 Cell Line.Iranian biomedical journal · 2024Article
- Combination of metformin and gallic acid induces autophagy and apoptosis in human breast cancer cells.Research in pharmaceutical sciences · 2023Article
- Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells.Pharmaceutical biology · 2023Article
- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
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- Targeting casein kinase 1 for cancer therapy: current strategies and future perspectives.Frontiers in oncology · 2023Review
- Potential role of TGFΒ and autophagy in early crebellum development.Biochemistry and biophysics reports · 2022Article
- CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes.Cancers · 2022Review
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11 authors at 3 institutions in 3 countries.
Funding
Abstract
Adjuvant chemotherapy with 5-fluorouracil (5-FU) does not improve survival of patients suffering from a form of colorectal cancer (CRC) characterized by high level of microsatellite instability (MSI-H). Given the importance of autophagy and multi-drug-resistant (MDR) proteins in chemotherapy resistance, as well as the role of casein kinase 1-alpha (CK1α) in the regulation of autophagy, we tested the combined effect of 5-FU and CK1α inhibitor (D4476) on HCT116 cells as a model of MSI-H colorectal cancer. To achieve this goal, the gene expression of Beclin1 and MDR genes, ABCG2 and ABCC3 were analyzed using quantitative real-time polymerase chain reaction. We used immunoblotting to measure autophagy flux (LC3, p62) and flow cytometry to detect apoptosis. Our findings showed that combination treatment with 5-FU and D4476 inhibited autophagy flux. Moreover, 5-FU and D4476 combination therapy induced G2, S and G1 phase arrests and it depleted mRNA of both cell proliferation-related genes and MDR-related genes (ABCG2, cyclin D1 and c-myc). Hence, our data indicates that targeting of CK1α may increase the sensitivity of HCT116 cells to 5-FU. To our knowledge, this is the first description of sensitization of CRC cells to 5-FU chemotherapy by CK1α inhibitor.
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