Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression

David W. Sant, Sushmita Mustafi, Christopher B. Gustafson, Joshua Chen, Joyce M Slingerland, Gaofeng Wang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Genomic loss of 5-hydroxymethylcytosine (5hmC) accompanies malignant cellular transformation in breast cancer. Vitamin C serves as a cofactor for TET methylcytosine dioxygenases to increase 5hmC generation. Here we show that the transcription of SVCT2, a major vitamin C transporter, was decreased in human breast cancers (113 cases) compared to normal breast tissues from the same patients. A decreased SVCT2 expression was also observed in breast cancer cell lines. Treatment with vitamin C (100 μM) increased the 5hmC content in MDA-MB-231 breast cancer cells and markedly altered the transcriptome. The vitamin C treatment induced apoptosis in MDA-MB-231 cells, which was verified in two additional breast cancer cell lines. This pro-apoptotic effect of vitamin C appeared to be mediated by TRAIL, a known apoptosis inducer. Vitamin C upregulated TRAIL transcripts (2.3-fold increase) and increased TRAIL protein levels. The upregulation of TRAIL by vitamin C was largely abolished by siRNAs targeting TETs and anti-TRAIL antibody abrogated the induction of apoptosis. Furthermore, the apoptosis promoted by vitamin C was associated with Bax and caspases activation, Bcl-xL sequestration, and cytochrome c release. Taken together, these results suggest a potential role of physiological doses of vitamin C in breast cancer prevention and treatment.

Original languageEnglish (US)
Article number5306
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Ascorbic Acid
Apoptosis
Breast Neoplasms
TNF-Related Apoptosis-Inducing Ligand
Dioxygenases
Cell Line
Caspases
Cytochromes c
Transcriptome
Anti-Idiotypic Antibodies
Breast
Up-Regulation
Therapeutics
5-hydroxymethylcytosine

ASJC Scopus subject areas

  • General

Cite this

Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression. / Sant, David W.; Mustafi, Sushmita; Gustafson, Christopher B.; Chen, Joshua; Slingerland, Joyce M; Wang, Gaofeng.

In: Scientific Reports, Vol. 8, No. 1, 5306, 01.12.2018.

Research output: Contribution to journalArticle

Sant, David W. ; Mustafi, Sushmita ; Gustafson, Christopher B. ; Chen, Joshua ; Slingerland, Joyce M ; Wang, Gaofeng. / Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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