Restoration of 5‐hydroxymethylcytosine by ascorbate blocks kidney tumour growth
| العنوان: | Restoration of 5‐hydroxymethylcytosine by ascorbate blocks kidney tumour growth |
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| المؤلفون: | Liqun Zhou, Bao Guan, Weimin Ci, Xuesong Li, Yuanyuan Zhou, Ding Peng, Ziying Xu, Qun He, Guangzhe Ge, Zijuan Xin |
| المصدر: | EMBO reports. 19 |
| بيانات النشر: | EMBO, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Ascorbic Acid, Biology, Biochemistry, Dioxygenases, Transcriptome, Mice, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Differentiation therapy, In vivo, Cell Line, Tumor, Proto-Oncogene Proteins, Genetics, medicine, Animals, Humans, Kidney tumour, Carcinoma, Renal Cell, Molecular Biology, Cell Proliferation, Kidney, Articles, medicine.disease, Xenograft Model Antitumor Assays, Kidney Neoplasms, DNA-Binding Proteins, Clear cell renal cell carcinoma, Enhancer Elements, Genetic, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, 5-Methylcytosine, Cancer research, Reprogramming |
| الوصف: | Loss of 5‐hydroxymethylcytosine (5hmC) occurs frequently in a wide variety of tumours, including clear‐cell renal cell carcinoma (ccRCC). It remains unknown, however, whether the restoration of 5hmC patterns in tumours could have therapeutic efficacy. Here, we used sodium L‐ascorbate (vitamin C, AsANa) and the oxidation‐resistant form L‐ascorbic acid 2‐phosphate sesquimagnesium (APM) for the restoration of 5hmC patterns in ccRCC cells. At physiological concentrations, both show anti‐tumour efficacy during long‐term treatment in vitro and in vivo. Strikingly, global 5hmC patterns in ccRCC cells after treatment resemble those of normal kidney tissue, which is observed also in treated xenograft tumours, and in primary cells from a ccRCC patient. Further, RNA‐seq data show that long‐term treatment with vitamin C changes the transcriptome of ccRCC cells. Finally, APM treatment induces less non‐specific cell damage and shows increased stability in mouse plasma compared to AsANa. Taken together, our study provides proof of concept for an epigenetic differentiation therapy of ccRCC with vitamin C, especially APM, at low doses by 5hmC reprogramming. |
| تدمد: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201745401 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b77f590a0dac27bf65ed815e359ba13 https://doi.org/10.15252/embr.201745401 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7b77f590a0dac27bf65ed815e359ba13 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14693178 1469221X |
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| DOI: | 10.15252/embr.201745401 |