ArticleOncoTargets and therapy2018
Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Endothelial Dysfunction and Metabolic Reprogramming in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- Plant-Derived Compounds as Potential Sensitizers to Immunotherapy in Melanoma.International journal of molecular sciences · 2026Review
- Dietary Polyphenols Curcumin and Resveratrol Exert Selective Anticancer Effects in Melanoma Cells.Nutrients · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Targeting cancer hallmarks using resveratrol: isolation, formulation, and mechanisms of action.Frontiers in nutrition · 2026Review
- Comprehensive analysis based on spatial domains identifies CD44 as a potential target of puerarin.Journal of cancer research and clinical oncology · 2025Article
- Major Plant-Based Compounds for the Prevention and Treatment of Melanoma-A Mini Review.Biology · 2025Review
- Review
- Natural products as therapeutics for malignant melanoma: preclinical evidence and mechanism.Frontiers in pharmacology · 2025Review
- A recent update on the connection between dietary phytochemicals and skin cancer: emerging understanding of the molecular mechanism.Annals of medicine and surgery (2012) · 2024Review
- Resveratrol-Enriched Rice Callus Extract Inhibits Oxidative and Cellular Melanogenic Activities in Melan-A Cells.Antioxidants (Basel, Switzerland) · 2024Article
- FV-429 induces apoptosis by regulating nuclear translocation of PKM2 in pancreatic cancer cells.Heliyon · 2024Article
- Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis.Archives of medical science : AMS · 2024Article
- Bitter Phytochemicals as Novel Candidates for Skin Disease Treatment.Current issues in molecular biology · 2023Review
- Resveratrol May Reduce the Degree of Periodontitis by Regulating ERK Pathway in Gingival-Derived MSCs.International journal of molecular sciences · 2023Article
- Morusin shows potent antitumor activity for melanoma through apoptosis induction and proliferation inhibition.BMC cancer · 2023Article
- Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms.Antioxidants (Basel, Switzerland) · 2023Review
- Resveratrol, Epigallocatechin Gallate and Curcumin for Cancer Therapy: Challenges from Their Pro-Apoptotic Properties.Life (Basel, Switzerland) · 2023Review
- Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.Cancers · 2022Review
- Neuroprotective Effects of an Edible Pigment Brilliant Blue FCF against Behavioral Abnormity in MCAO Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResveratrol is known as a natural phytoalexin found in grapes and wine, which has significant antitumor activity under in vitro and in vivo conditions. In recent years, great progress has been made in understanding the underlying mechanisms of resveratrol in inducing cellular apoptosis of melanoma cells. Our previous study has shown that the apoptosis regulation of resveratrol in melanoma cells was independent of activation of classical apoptosis-related protein p53. MATERIALS AND
methodsMTT assay and 5-bromo-2'-deoxyuridine staining assay were used to analyze cell viability and proliferation. Immunofluorescence analysis of γ-H2AX was employed to clarify DNA damages. Annexin V-propidine iodide/fluorescein isothiocyanate assay was performed to evaluate the cell apoptosis. The mechanisms underlying the activation of M2-type pyruvate kinase (PKM2) by Erk1/2 to stabilize and maintain Bcl-2 signaling was investigated by subcellular fractionation analyses, immunofluorescence analysis, co-immunoprecipitation assay, ubiquitination assay, and glutathione S-transferase pull-down assay.
resultsIn the present study, we found that resveratrol dramatically inhibited melanoma cell proliferation and induced cell apoptosis through upregulation of p53 in a concentration-dependent manner. Conversely, p53 downregulation by short hairpin RNA couldn't rescue resveratrol-induced cell proliferation inhibition or apoptosis enlargement. Additionally, we found that resveratrol downregulated antiapoptotic protein Bcl-2 and activated Bax in the protein levels by promoting Bcl-2 degradation and cytochrome c release. Moreover, we discovered that PKM2, had a key role in cell apoptosis triggered by resveratrol through interacting with Bcl-2. Based on these results, we overexpressed PKM2 in melanoma cells and found that this prevented resveratrol-induced apoptosis by stabilizing the protein level of Bcl-2.
conclusionTaken together, our results provided a novel mechanism accounting for the apoptosis induction of resveratrol in melanoma cells and suggested that downregulating Erk/PKM2/Bcl-2 axis appears to be a new approach for the prevention or treatment of melanoma.
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