ArticleMolecular carcinogenesis2015
Honokiol inhibits melanoma stem cells by targeting notch signaling.
Article in Molecular carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 76 citations in OpenAlex.
- Natural medicines target tumor vascular microenvironment to inhibit tumor.Genes & diseases · 2025Review
- Antibacterial, Photoprotective, Anti-Inflammatory, and Selected Anticancer Properties of Honokiol Extracted from Plants of the GenusInternational journal of molecular sciences · 2025Review
- Research Progress of Natural Compounds from Chinese Herbal Medicine in the Treatment of Melanoma.Current treatment options in oncology · 2025Review
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Notch signaling pathway modulation by food functional ingredients: mechanisms, cancer and immunoregulation.Frontiers in cell and developmental biology · 2025Review
- Article
- Autophagy as a targeted therapeutic approach for skin cancer: Evaluating natural and synthetic molecular interventions.Cancer pathogenesis and therapy · 2024Review
- Review
- Honokiol-RichAntioxidants (Basel, Switzerland) · 2023Article
- Autophagic mechanisms in longevity intervention: role of natural active compounds.Expert reviews in molecular medicine · 2023Review
- The application prospects of honokiol in dermatology.Dermatologic therapy · 2022Review
- 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
- Article
- Effect of melanoma stem cells on melanoma metastasis.Oncology letters · 2021Review
- Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches.Molecules (Basel, Switzerland) · 2021Article
- Celastrol and Triptolide Suppress Stemness in Triple Negative Breast Cancer: Notch as a Therapeutic Target for Stem Cells.Biomedicines · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Melanoma is an aggressive disease with limited therapeutic options. Here, we determined the effects of honokiol (HNK), a biphenolic natural compound on melanoma cells and stemness. HNK significantly inhibited melanoma cell proliferation, viability, clonogenicity and induced autophagy. In addition, HNK significantly inhibited melanosphere formation in a dose dependent manner. Western blot analyses also demonstrated reduction in stem cell markers CD271, CD166, Jarid1b, and ABCB5. We next examined the effect of HNK on Notch signaling, a pathway involved in stem cell self-renewal. Four different Notch receptors exist in cells, which when cleaved by a series of enzymatic reactions catalyzed by Tumor Necrosis Factor-α-Converting Enzyme (TACE) and γ-secretase protein complex, results in the release of the Notch intracellular domain (NICD), which then translocates to the nucleus and induces target gene expression. Western blot analyses demonstrated that in HNK treated cells there is a significant reduction in the expression of cleaved Notch-2. In addition, there was a reduction in the expression of downstream target proteins, Hes-1 and cyclin D1. Moreover, HNK treatment suppressed the expression of TACE and γ-secretase complex proteins in melanoma cells. To confirm that suppression of Notch-2 activation is critical for HNK activity, we overexpressed NICD1, NICD2, and performed HNK treatment. NICD2, but not NICD1, partially restored the expression of Hes-1 and cyclin D1, and increased melanosphere formation. Taken together, these data suggest that HNK is a potent inhibitor of melanoma cells, in part, through the targeting of melanoma stem cells by suppressing Notch-2 signaling.
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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.