ArticleExperimental cell research2008
Resveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression.
Article in Experimental cell research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy.Frontiers in oncology · 2022Pooled it
- NAD+ metabolism and therapeutic strategies in cardiovascular diseases.Atherosclerosis plus · 2024Review
- Phytochemicals as Immunomodulatory Molecules in Cancer Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Astaxanthin improves fatty acid dysregulation in diabetes by controlling the AMPK-SIRT1 pathway.EXCLI journal · 2023Article
- Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.Frontiers in immunology · 2021Review
- Influence of Resveratrol on the Immune Response.Nutrients · 2019Review
- Mitochondrial targeting by dichloroacetate improves outcome following hemorrhagic shock.Scientific reports · 2017Article
- Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells.Oncotarget · 2017Article
- Drosophila imaginal disc growth factor 2 is a trophic factor involved in energy balance, detoxification, and innate immunity.Scientific reports · 2017Article
- Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra.Current genomics · 2017Review
- Slowing ageing by design: the rise of NADNature reviews. Molecular cell biology · 2016Review
- Nutritional immunology: function of natural killer cells and their modulation by resveratrol for cancer prevention and treatment.Nutrition journal · 2016Review
- South Asian Medicinal Compounds as Modulators of Resistance to Chemotherapy and Radiotherapy.Cancers · 2016Review
- Phytochemicals for the Management of Melanoma.Mini reviews in medicinal chemistry · 2016Review
- Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells.The Journal of investigative dermatology · 2014Article
- ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis.Cell death & disease · 2013Article
- Computational modelling of LY303511 and TRAIL-induced apoptosis suggests dynamic regulation of cFLIP.Bioinformatics (Oxford, England) · 2013Article
- Sensitization of melanoma cells for TRAIL-induced apoptosis by BMS-345541 correlates with altered phosphorylation and activation of Bax.Cell death & disease · 2013Article
- SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function.Cell metabolism · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although many human melanomas express the death receptors TRAIL-R2/DR5 or TRAIL-R1/DR4 on cell surface, they often exhibit resistance to exogenous TRAIL. One of the main contributors to TRAIL-resistance of melanoma cells is upregulation of transcription factors STAT3 and NF-kappaB that control the expression of antiapoptotic genes, including cFLIP and Bcl-xL. On the other hand, the JNK-cJun pathway is involved in the negative regulation of cFLIP (a caspase-8 inhibitor) expression. Our observations indicated that resveratrol, a polyphenolic phytoalexin, decreased STAT3 and NF-kappaB activation, while activating JNK-cJun that finally suppressed expression of cFLIP and Bcl-xL proteins and increased sensitivity to exogenous TRAIL in DR5-positive melanomas. Interestingly, resveratrol did not increase surface expression of DR5 in human melanomas, while gamma-irradiation or sodium arsenite treatment substantially upregulated DR5 expression. Hence, an initial increase in DR5 surface expression (either by gamma-irradiation or arsenite), and subsequent downregulation of antiapoptotic cFLIP and Bcl-xL (by resveratrol), appear to constitute an efficient approach to reactivate apoptotic death pathways in TRAIL-resistant human melanomas. In spite of partial suppression of mitochondrial function and the mitochondrial death pathway, melanoma cells still retain the potential to undergo the DR5-mediated, caspase-8-dependent death pathway that could be accelerated by either an increase in DR5 surface expression or suppression of cFLIP. Taken together, these results suggest that resveratrol, in combination with TRAIL, may have a significant efficacy in the treatment of human melanomas.
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Registered trials
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