ArticlePloS one2016
Muscadine Grape Skin Extract Induces an Unfolded Protein Response-Mediated Autophagy in Prostate Cancer Cells: A TMT-Based Quantitative Proteomic Analysis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Muscadine Grape Skin Extract (MPX) in Men with Biochemically Recurrent Prostate Cancer: A Randomized, Multicenter, Placebo-Controlled Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Oncogenic Proteomics Approaches for Translational Research and HIV-Associated Malignancy Mechanisms.Proteomes · 2023Review
- Regulation of plants developed through new breeding techniques must ensure societal benefits.Nature plants · 2023Article
- Article
- The endoplasmic reticulum stress response in prostate cancer.Nature reviews. Urology · 2022Review
- MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells.Journal of radiation research · 2021Article
- Val16A SOD2 Polymorphism Promotes Epithelial-Mesenchymal Transition Antagonized by Muscadine Grape Skin Extract in Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2021Article
- Grape Powder Supplementation Attenuates Prostate Neoplasia Associated with Pten Haploinsufficiency in Mice Fed High-Fat Diet.Molecular nutrition & food research · 2020Article
- PPARδ is a regulator of autophagy by its phosphorylation.Oncogene · 2020Article
- Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies.Antioxidants (Basel, Switzerland) · 2019Review
- Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response.International journal of molecular sciences · 2019Review
- Synergistic Action of Stilbenes in Muscadine Grape Berry Extract Shows Better Cytotoxic Potential Against Cancer Cells Than Resveratrol Alone.Biomedicines · 2019Article
- Phytochemicals in Prostate Cancer: From Bioactive Molecules to Upcoming Therapeutic Agents.Nutrients · 2019Review
- Proteomics-Metabolomics Combined Approach Identifies Peroxidasin as a Protector against Metabolic and Oxidative Stress in Prostate Cancer.International journal of molecular sciences · 2019Article
- Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells.Cancer letters · 2019Article
- Multi-year Quantitative Evaluation of Stilbenoids Levels Among Selected Muscadine Grape Cultivars.Molecules (Basel, Switzerland) · 2019Article
- The ER-localized CaThe Journal of biological chemistry · 2019Article
- Article
- Polyphenol Extracts from Red Wine and Grapevine: Potential Effects on Cancers.Diseases (Basel, Switzerland) · 2018Review
- Effect of Ball Mill Treatment on the Physicochemical Properties and Digestibility of Protein Extracts Generated from Scallops (Chlamys farreri).International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Muscadine grape skin extract (MSKE) is derived from muscadine grape (Vitis rotundifolia), a common red grape used to produce red wine. Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy. We hypothesized that MSKE may induce a severe ER stress response-mediated autophagy leading to apoptosis. As a model, we treated C4-2 prostate cancer cells with MSKE and performed a quantitative Tandem Mass Tag Isobaric Labeling proteomic analysis. ER stress response, autophagy and apoptosis were analyzed by western blot, acridine orange and TUNEL/Annexin V staining, respectively. Quantitative proteomics analysis indicated that ER stress response proteins, such as GRP78 were greatly elevated following treatment with MSKE. The up-regulation of pro-apoptotic markers PARP, caspase-12, cleaved caspase-3, -7, BAX and down-regulation of anti-apoptotic marker BCL2 was confirmed by Western blot analysis and apoptosis was visualized by increased TUNEL/Annexin V staining upon MSKE treatment. Moreover, increased acridine orange, and LC3B staining was detected in MSKE-treated cells, suggesting an ER stress/autophagy response. Finally, MSKE-mediated autophagy and apoptosis was antagonized by co-treatment with chloroquine, an autophagy inhibitor. Our results indicate that MSKE can elicit an UPR that can eventually lead to apoptosis in prostate cancer cells.
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Registered trials
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