Vitamin C Protects Against UV Irradiation-Induced Apoptosis Through Reactivating Silenced Tumor Suppressor Genes p21 and p16 in a Tet-Dependent DNA Demethylation Manner in Human Skin Cancer Cells
Abstract
Aim DNA methylation plays important roles in various kinds of carcinogenesis. Vitamin C could induce Tet-dependent DNA demethylation in embryonic stem cells. Therefore, the antagonizing activity of vitamin C on ultraviolet (UV)-induced apoptosis was investigated in this study. Methods Apoptosis of human epidermoid carcinoma A431 cells and p16-knockout (KO) or p21-KO fibroblasts was assessed by a fluorescence-activated cell sorter. Real-time PCR and western blot were used to determine the relative expression levels of p12, p21, and Tet1/2/3 genes. The global DNA methylation levels were determined using MethylFlash Methylated DNA Quantification Kit in A431 cells with or without vitamin C treatment. To examine the DNA demethylation activity of vitamin C, DNA immunoprecipitation (DIP)-qPCR was performed to determine the relative levels of 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) in p16 and p21 promoter regions containing cytosine-phosphorothiolated guanine (CpG) islands. Results The increasing apoptosis of A431 cells under prolonged UV irradiation was remarkably decreased by the combination of vitamin C treatment, suggesting that vitamin C protects against UV-induced apoptosis. Concurrently, vitamin C induced a significant reduction of global DNA methylation in a time- and dose-dependent manner in A431 cells. Vitamin C also reactivated the expression of p16 and p21 at mRNA and protein levels. Mechanistically, about 27% 5hmC-positive cells were observed in vitamin…
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Vitamin C protected against UV-induced apoptosis of an epidermal cell line via a TET-dependent mechanism, which involved increases in p21 and p16 gene expression.
“For example, Lin and co-workers showed that vitamin C protected against UV-induced apoptosis of an epidermal cell line via a TET-dependent mechanism, which involved increases in p21 and p16 gene expression [117].”
From The Roles of Vitamin C in Skin Health. (2017) · cites this paper as [117]
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The Roles of Vitamin C in Skin Health.
Pullar, J., Carr, A., & Vissers, M. (2017) · Nutrients · doi:10.3390/nu9080866 · Cited by 756 · see citing works
“For example, Lin and co-workers showed that vitamin C protected against UV-induced apoptosis of an epidermal cell line via a TET-dependent mechanism, which involved increases in p21 and p16 gene expression [117].”
BackgroundQin, D., Lee, W.-H., Gao, Z., Zhang, W., Peng, M., Sun, T., & Gao, Y. (2018) · Peptides · doi:10.1016/j.peptides.2018.01.009 · Cited by 27 · see citing works
- Authors
- Lin, J.-R., Qin, H.-H., Wu, W.-Y., He, S.-J., & Xu, J.-H.
- Affiliations
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
- College of Animal Sciences, Zhejiang University, China.
- Venue
- Cancer Biotherapy and Radiopharmaceuticals
- Publisher
- SAGE Publications
- Published
- 2014-08
- Volume
- 29
- Issue
- 6
- Pages
- 257-264
- ISSN
- 1084-9785 (ISSN-L)
- 1557-8852
- OpenAlex
- W1894876564
- Cited by
- 37
- References
- 2
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 2
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Biotherapy and Radiopharmaceuticals (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Keywords
- vitamin C, UV-induced apoptosis, DNA demethylation, TET enzymes, p16, p21, tumor suppressor gene reactivation, 5-hydroxymethylcytosine, 5-methylcytosine, global DNA methylation, skin cancer, A431 cells, squamous cell carcinoma, CpG islands
- MeSH terms
- Animals, Ascorbic Acid, Humans, Neoplasm Proteins, Skin Neoplasms, Transfection, Ultraviolet Rays, Genes, Tumor Suppressor, Apoptosis, Mice, Knockout, DNA Methylation, Cyclin-Dependent Kinase Inhibitor p16, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Gene Knockout Techniques
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