ArticleMolecular cancer therapeutics2012
Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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
55 citing papers in PubMed, 106 citations in OpenAlex.
- From Aryltetralin Anticancer Scaffolds to Host-Directed Bioactivities: A Mechanism-Based Review of Lignans and Neolignans.International journal of molecular sciences · 2026Review
- Review
- Notch signaling pathway modulation by food functional ingredients: mechanisms, cancer and immunoregulation.Frontiers in cell and developmental biology · 2025Review
- Article
- Upregulation of tumor suppressor PIAS3 by Honokiol promotes tumor cell apoptosis via selective inhibition of STAT3 tyrosine 705 phosphorylation.Journal of natural medicines · 2024Article
- Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.Frontiers in pharmacology · 2024Review
- Colorectal Cancer Stem Cells and Targeted Agents.Pharmaceutics · 2023Review
- Semisynthesis and anti-cancer properties of novel honokiol derivatives in human nasopharyngeal carcinoma CNE-2Z cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Cancer stem cells and their niche in cancer progression and therapy.Cancer cell international · 2023Review
- Article
- Honokiol-RichAntioxidants (Basel, Switzerland) · 2023Article
- Active Ingredients from Chinese Medicine for Combination Cancer Therapy.International journal of biological sciences · 2023Review
- Targeting Annexin A1 as a Druggable Player to Enhance the Anti-Tumor Role of Honokiol in Colon Cancer through Autophagic Pathway.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Modulation of Notch Signaling Pathway by Bioactive Dietary Agents.International journal of molecular sciences · 2022Review
- Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen.Frontiers in oncology · 2022Article
- Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.Cancer communications (London, England) · 2021Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Honokiol Affects Stem Cell Viability by Suppressing Oncogenic YAP1 Function to Inhibit Colon Tumorigenesis.Cells · 2021Article
- Radiosensitization of NSCLC cells to X-rays and carbon ions by the CHK1/CHK2 inhibitor AZD7762, Honokiol and Tunicamycin.Radiation and environmental biophysics · 2020Article
- Emerging Nanopharmaceuticals and Nanonutraceuticals in Cancer Management.Biomedicines · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Cancer stem cells are implicated in resistance to ionizing radiation (IR) and chemotherapy. Honokiol, a biphenolic compound has been used in traditional Chinese medicine for treating various ailments. In this study, we determined the ability of honokiol to enhance the sensitivity of colon cancer stem cells to IR. The combination of honokiol and IR suppressed proliferation and colony formation while inducing apoptosis of colon cancer cells in culture. There were also reduced numbers and size of spheroids, which was coupled with reduced expression of cancer stem cell marker protein DCLK1. Flow cytometry studies confirmed that the honokiol-IR combination reduced the number of DCLK1+ cells. In addition, there were reduced levels of activated Notch-1, its ligand Jagged-1, and the downstream target gene Hes-1. Furthermore, expression of components of the Notch-1 activating γ-secretase complex, presenilin 1, nicastrin, Pen2, and APH-1 was also suppressed. On the other hand, the honokiol effects were mitigated when the Notch intracellular domain was expressed. To determine the effect of honokiol-IR combination on tumor growth in vivo, nude mice tumor xenografts were administered honokiol intraperitoneally and exposed to IR. The honokiol-IR combination significantly inhibited tumor xenograft growth. In addition, there were reduced levels of DCLK1 and the Notch signaling-related proteins in the xenograft tissues. Together, these data suggest that honokiol is a potent inhibitor of colon cancer growth that targets the stem cells by inhibiting the γ-secretase complex and the Notch signaling pathway. These studies warrant further clinical evaluation for the combination of honokiol and IR for treating colon cancers.
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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.