ArticleJournal of experimental & clinical cancer research : CR2019
Melatonin synergizes BRAF-targeting agent vemurafenib in melanoma treatment by inhibiting iNOS/hTERT signaling and cancer-stem cell traits.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
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- Melatonin Synergises the Chemotherapeutic Effect of Temozolomide in Glioblastoma by Suppressing NF-κB/COX-2 Signalling Pathways.Journal of cellular and molecular medicine · 2025Article
- Melatonin and the Skin: Current Progress and Perspectives for Human Health.The Journal of investigative dermatology · 2025Review
- Melatonin Interplay in Physiology and Disease-The Fountain of Eternal Youth Revisited.Biomolecules · 2025Review
- Melatonin combined with antineoplastic drugs or natural products for cancer treatment: An update.Current research in pharmacology and drug discovery · 2025Review
- Correction: Melatonin synergizes BRAF-targeting agent vemurafenib in melanoma treatment by inhibiting iNOS/hTERT signaling and cancer-stem cell traits.Journal of experimental & clinical cancer research : CR · 2024Article
- Self-assembled gel microneedle formed by MS deep eutectic solvent as a transdermal delivery system for hyperpigmentation treatment.Materials today. Bio · 2024Article
- Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer.Molecular medicine reports · 2024Article
- Evaluation of Melatonin and its Nanostructures Effects on Skin Disorders Focused on Wound Healing.Mini reviews in medicinal chemistry · 2024Review
- Melatonin as a Repurposed Drug for Melanoma Treatment.Medical sciences (Basel, Switzerland) · 2023Review
- Mechanism of action and promising clinical application of melatonin from a dermatological perspective.Journal of translational autoimmunity · 2023Article
- The ubiquitin-specific protease 8 antagonizes melatonin-induced endocytic degradation of MTJournal of advanced research · 2022Article
- Use of Melatonin in Cancer Treatment: Where Are We?International journal of molecular sciences · 2022Review
- MiR-138-5p Suppresses Cell Growth and Migration in Melanoma by Targeting Telomerase Reverse Transcriptase.Genes · 2021Article
- Melatonin and neuroblastoma: a novel therapeutic approach.Molecular biology reports · 2021Review
- SPT6 recruits SND1 to co-activate human telomerase reverse transcriptase to promote colon cancer progression.Molecular oncology · 2021Article
- Melatonin sensitizes esophageal cancer cells to 5‑fluorouracil via promotion of apoptosis by regulating EZH2 expression.Oncology reports · 2021Article
- An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress.Cancer cell international · 2021Review
- V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) as a prognostic biomarker of poor outcomes in esophageal cancer patients.BMC gastroenterology · 2021Article
- Role and Therapeutic Potential of Melatonin in Various Type of Cancers.OncoTargets and therapy · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundAs the selective inhibitor of BRAF kinase, vemurafenib exhibits effective antitumor activities in patients with V600 BRAF mutant melanomas. However, acquired drug resistance invariably develops after its initial treatment.
methodsImmunohistochemical staining was performed to detect the expression of iNOS and hTERT, p-p65, Epcam, CD44, PCNA in mice with melanoma xenografts. The proliferation and migration of melanoma cells were detected by MTT, tumorsphere culture, cell cycle, cell apoptosis, AO/EB assay and colony formation, transwell assay and scratch assay in vitro, and tumor growth differences were observed in xenograft nude mice. Changes in the expression of key molecules in the iNOS/hTERT signaling pathways were detected by western blot. Nucleus-cytoplasm separation, and immunofluorescence analyses were conducted to explore the location of p50/p65 in melanoma cell lines. Flow cytometry assay were performed to determine the expression of CD44. Pull down assay and ChIP assay were performed to detect the binding ability of p65 at iNOS and hTERT promoters. Additionally, hTERT promoter-driven luciferase plasmids were transfected in to melanoma cells with indicated treatment to determine luciferase activity of hTERT.
resultsMelatonin significantly and synergistically enhanced vemurafenib-mediated inhibitions of proliferation, colony formation, migration and invasion and promoted vemurafenib-induced apoptosis, cell cycle arresting and stemness weakening in melanoma cells. Further mechanism study revealed that melatonin enhanced the antitumor effect of vemurafenib by abrogating nucleus translocation of NF-κB p50/p65 and their binding at iNOS and hTERT promoters, thereby suppressing the expression of iNOS and hTERT. The elevated anti-tumor capacity of vemurafenib upon co-treatment with melatonin was also evaluated and confirmed in mice with melanoma xenografts.
conclusionsCollectively, our results demonstrate melatonin synergizes the antitumor effect of vemurafenib in human melanoma by inhibiting cell proliferation and cancer-stem cell traits via targeting NF-κB/iNOS/hTERT signaling pathway, and suggest the potential of melatonin in antagonizing the toxicity of vemurafenib and augmenting its sensitivities in melanoma treatment.
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