Vitamin C in Stem Cell Reprogramming and Cancer. Issue 9 (September 2018)

• Record Type: Journal Article
• Authors: Cimmino, Luisa; Neel, Benjamin G.; Aifantis, Iannis
• Is Part Of: Trends in cell biology. Volume 28:Issue 9(2018)
• Page Start: 698
• Page End: 708
• Publication Date: 2018-09
• Subjects: vitamin C -- epigenetics -- stem cells -- TET proteins -- methylation -- cancer; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2018.04.001
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Vitamin C is an essential dietary requirement for humans. In addition to its known role as an antioxidant, vitamin C is a cofactor for Fe 2+ - and α-ketoglutarate-dependent dioxygenases (Fe 2+ /α-KGDDs) which comprise a large number of diverse enzymes, including collagen prolyl hydroxylases and epigenetic regulators of histone and DNA methylation. Vitamin C can modulate embryonic stem cell (ESC) function, enhance reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs), and hinder the aberrant self-renewal of hematopoietic stem cells (HSCs) through its ability to enhance the activity of either Jumonji C (JmjC) domain-containing histone demethylases or ten-eleven translocation (TET) DNA hydroxylases. Given that epigenetic dysregulation is a known driver of malignancy, vitamin C may play a novel role as an epigenetic anticancer agent. Highlights: Vitamin C is essential for humans, and plasma levels are tightly controlled by sodium-dependent vitamin C transporters that are responsible for dietary absorption and whole-body uptake. Vitamin C is an antioxidant and a cofactor for Fe 2+ /α-KGDDs. Vitamin C enhances epigenetic reprogramming of fibroblasts to iPSCs, and maintains ESC pluripotency, by regulating the activity of JmjC domain-containing histone demethylases and TET hydroxylases. Vitamin C deficiency can promote aberrant self-renewal in HSCs and accelerate leukemia progression by decreasing the activity of TET hydroxylases. Pharmacological doses of vitamin C can restore TET function in HSCs, and may represent a promising adjuvant to standard therapies for the treatment of leukemia and other cancers.