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Updated: Feb 8, 2026

Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
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Restoration of 5-hydroxymethylcytosine by ascorbate blocks kidney tumour growth

Guangzhe Ge1,2, Ding Peng1,3,4,5, Ziying Xu1,2

  • 1Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

EMBO Reports
|July 1, 2018
PubMed

Insights

Restoring 5-hydroxymethylcytosine (5hmC) patterns in clear-cell renal cell carcinoma (ccRCC) using vitamin C (ascorbate) showed anti-tumour effects. This epigenetic therapy reprogrammed ccRCC cells, resembling normal kidney tissue patterns.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Biochemistry

Background:

  • Loss of 5-hydroxymethylcytosine (5hmC) is common in clear-cell renal cell carcinoma (ccRCC).
  • The therapeutic potential of restoring 5hmC patterns in ccRCC remains largely unexplored.

Purpose of the Study:

  • To investigate the efficacy of vitamin C (ascorbate) in restoring 5hmC patterns in ccRCC.
  • To evaluate the anti-tumour effects of vitamin C and its derivatives in ccRCC treatment.

Main Methods:

  • Treatment of ccRCC cells and xenografts with sodium L-ascorbate (AsANa) and L-ascorbic acid 2-phosphate sesquimagnesium (APM).
  • Analysis of 5hmC patterns, transcriptome changes (RNA-seq), and cell damage.
  • In vitro and in vivo efficacy assessments.

Main Results:

  • Both AsANa and APM demonstrated anti-tumour efficacy at physiological concentrations.
  • Vitamin C treatment restored 5hmC patterns in ccRCC cells to resemble normal kidney tissue.
  • Long-term vitamin C treatment altered the ccRCC cell transcriptome.
  • APM showed greater stability and less non-specific cell damage compared to AsANa.

Conclusions:

  • Vitamin C, particularly APM, shows potential as an epigenetic differentiation therapy for ccRCC.
  • 5hmC reprogramming by low-dose vitamin C offers a novel therapeutic strategy for ccRCC.
Keywords:
5‐hydroxymethylcytosineclear‐cell renal cell carcinomadifferentiationepigenetic reprogrammingvitamin C

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