ArticleScientific reports2017
Ascorbate induces apoptosis in melanoma cells by suppressing Clusterin expression.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Comparative Proteomic Analysis of the Secretome of Control and BRAF/MEK Inhibitor-Resistant Melanoma Cells.Journal of proteome research · 2026Article
- Review
- TET1 is a Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Papillary Thyroid Cancer.Biochemical genetics · 2024Article
- Clusterin: a marker and mediator of chemoresistance in colorectal cancer.Cancer metastasis reviews · 2024Review
- Clusterin: a double-edged sword in cancer and neurological disorders.EXCLI journal · 2024Review
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- Clusterin and Its Isoforms in Oral Squamous Cell Carcinoma and Their Potential as Biomarkers: A Comprehensive Review.Biomedicines · 2023Review
- A pan-cancer analysis reveals role of clusterin (Frontiers in genetics · 2022Article
- Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.Frontiers in oncology · 2022Review
- High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- The multiple roles and therapeutic potential of clusterin in non-small-cell lung cancer: a narrative review.Translational lung cancer research · 2021Review
- Review
- Aspirin inhibits hepatocellular carcinoma cell proliferation in vitro and in vivo via inducing cell cycle arrest and apoptosis.Oncology reports · 2020Article
- Two Faces of Vitamin C-Antioxidative and Pro-Oxidative Agent.Nutrients · 2020Review
- Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells.Biomolecules · 2020Review
- Serum Clusterin: A Potential Marker for Assessing the Clinical Severity and Short-Term Prognosis of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.Disease markers · 2020Article
- Plasma Vitamin C and Cancer Mortality in Kidney Transplant Recipients.Journal of clinical medicine · 2019Article
- Hepatomas are exquisitely sensitive to pharmacologic ascorbate (P-AscHTheranostics · 2019Article
- Vitamin C Sensitizes Melanoma to BET Inhibitors.Cancer research · 2018Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Pharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes. Here we show that 100 µM of ascorbate induced apoptosis in A2058 melanoma cells. RNA-seq analysis revealed that expression of the Clusterin (CLU) gene, which is related to apoptosis, was downregulated by ascorbate. The suppression of CLU was verified at transcript level in different melanoma cell lines, and at protein level in A2058 cells. The anti-apoptotic cytoplasmic CLU was decreased, while the pro-apoptotic nuclear CLU was largely maintained, after ascorbate treatment. These changes in CLU subcellular localization were also associated with Bax and caspases activation, Bcl-xL sequestration, and cytochrome c release. Taken together, this study establishes an impending therapeutic role of physiological ascorbate to potentiate apoptosis in melanoma.
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