ArticleCell death & disease2019
Combination of 5-fluorouracil and thymoquinone targets stem cell gene signature in colorectal cancer cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Nanoscale delivery systems for hepatocellular carcinoma: Functionalization, delivery strategies, and clinical challenges.Materials today. Bio · 2026Review
- A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression.Molecular oncology · 2026Article
- Cell Line-Dependent Cell Death Pathways Induced by Thymoquinone in Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- Swertiamarin fails to induce cytotoxicity in colon cancer cell lines: Evidence against a direct anticancer effect.PloS one · 2026Article
- Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.International journal of molecular sciences · 2025Review
- Multi-parametric magnetic resonance imaging evaluation of a novelQuantitative imaging in medicine and surgery · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Synergistic effects of abietic acid combined with doxorubicin on apoptosis induction in a human colorectal cancer cell line.Scientific reports · 2025Article
- Combination of 5-Fluorouracil and Thymoquinone for Enhanced Cytotoxicity, Genotoxicity and Apoptosis In Colorectal Cancer: In Vitro and In Vivo Studies.Journal of biochemical and molecular toxicology · 2025Article
- Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation.Journal of the Egyptian National Cancer Institute · 2025Article
- In Vitro Assessment of the Cytotoxic Effect of 5-Fluorouracil, Thymoquinone and their Combination on Tongue Squamous Cell Carcinoma Cell Line.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer.Current issues in molecular biology · 2023Review
- Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1.Molecules (Basel, Switzerland) · 2023Review
- ATF2 loss promotes 5-FU resistance in colon cancer cells via activation of the ATR-Chk1 damage response pathway.BMC cancer · 2023Article
- Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer.International journal of molecular sciences · 2023Review
- New Hybrid Scaffolds Based on 5-FU/Curcumin: Synthesis, Cytotoxic, Antiproliferative and Pro-Apoptotic Effect.Pharmaceutics · 2023Article
- The CAM Model-Q&A with Experts.Cancers · 2022Review
- Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2022Review
- Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone.International journal of molecular sciences · 2022Review
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Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5-fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
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