Vitamin C promotes decitabine or azacytidine induced DNA hydroxymethylation and subsequent reactivation of the epigenetically silenced tumour suppressor CDKN1A in colon cancer cells

Oncotarget
Christian GereckeBurkhard Kleuser

Abstract

Epigenetic silencing of tumour suppressor genes is a key hallmark of colorectal carcinogenesis. Despite this, the therapeutic potential of epigenetic agents capable of reactivating these silenced genes remains relatively unexplored. Evidence has shown the dietary antioxidant vitamin C (ascorbate) acts as an inducer of the ten-eleven translocation (TET) dioxygenases, an enzyme family that catalyses a recently described mechanism of DNA demethylation linked to gene re-expression. In this study, we set out to determine whether vitamin C can enhance the known anti-neoplastic actions of the DNA-demethylating agents decitabine (DAC) and azacytidine (AZA) in colorectal cancer cells. Administration of vitamin C alone significantly enhanced global levels of 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), without altering 5-methyl-2'-deoxycytidine (5-mdC), as would be expected upon the activation of TET dioxygenases. Concomitant treatment of vitamin C with either AZA or DAC resulted in an unexpectedly high increase of global 5-hmdC levels, one that administration of any these compounds alone could not achieve. Notably, this was also accompanied by increased expression of the tumour suppressor p21 (CDKN1A), and a significant increase in apopto...Continue Reading

References

Sep 17, 1992·Nature·S M PowellK W Kinzler
Jun 1, 1990·Cell·E R Fearon, B Vogelstein
Apr 15, 1964·Experientia·F SormJ Veselý
Jun 4, 2002·Nature Reviews. Genetics·Peter A Jones, Stephen B Baylin
Jun 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang QiaoPaul Dent
Mar 6, 2004·Cancer Metastasis Reviews·Yutaka Kondo, Jean-Pierre J Issa
Nov 5, 2004·World Journal of Gastroenterology : WJG·Xiao-Li XuJing-De Zhu
Feb 5, 2005·Palliative Medicine·Catriona R MaylandKeith Allan
Mar 16, 2005·The American Journal of Surgical Pathology·Lucian R ChirieacStanley R Hamilton
Mar 29, 2005·The Oncologist·Edvardas KaminskasRichard Pazdur
Sep 7, 2005·Gastroenterology·Jean-Pierre J IssaMinoru Toyota
Dec 14, 2006·Expert Opinion on Pharmacotherapy·Ehab AtallahGuillermo Garcia-Manero
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lanlan ShenJean-Pierre J Issa
Dec 18, 2007·Nucleic Acids Research·Jairo RodriguezMiguel A Peinado
Mar 25, 2008·Therapeutics and Clinical Risk Management·Kavita Raj, Ghulam J Mufti
Apr 22, 2008·International Journal of Cancer. Journal International Du Cancer·Carlo Stresemann, Frank Lyko
Sep 4, 2008·Genes, Chromosomes & Cancer·Carol SweeneyMartha L Slattery
Dec 23, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pierre FenauxLewis R Silverman
Nov 26, 2010·Annual Review of Pathology·Eric R Fearon
Dec 15, 2010·Progress in Drug Research. Fortschritte Der Arzneimittelforschung. Progrès Des Recherches Pharmaceutiques·Phillippa C Taberlay, Peter A Jones
Apr 15, 2011·The Journal of Clinical Investigation·Eveline J SteineHeinz G Linhart
Oct 20, 2011·Nature Reviews. Gastroenterology & Hepatology·Victoria Valinluck Lao, William M Grady
Jun 26, 2012·Biochimica Et Biophysica Acta·Juan DuGarry R Buettner
Sep 18, 2012·Cell·Christine Guo LianYujiang G Shi
Nov 10, 2012·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yukari TakahashiMasahiko Okano

❮ Previous
Next ❯

Citations

May 18, 2019·Advances in Nutrition·McKale Montgomery, Aishwarya Srinivasan
Jan 15, 2020·Oxidative Medicine and Cellular Longevity·Elzbieta PawlowskaJanusz Blasiak
Aug 6, 2020·Journal for Immunotherapy of Cancer·Kirsty TaylorDaniel D De Carvalho
Aug 23, 2020·Antioxidants·Laura Bordoni, Rosita Gabbianelli
Sep 12, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Christian GereckeBurkhard Kleuser
Jun 30, 2019·World Journal of Gastroenterology : WJG·Zhen-Hua YangGuang Ji
Oct 19, 2019·British Journal of Pharmacology·Megan BeetchBarbara Stefanska
Oct 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sana WaheedViqar Syed
Oct 22, 2020·Critical Reviews in Food Science and Nutrition·Ankita KumariRajeev Kapila
Apr 1, 2021·Free Radical Biology & Medicine·Stine Ulrik MikkelsenKirsten Grønbæk
May 22, 2021·Frontiers in Genetics·John P BrabsonLuisa Cimmino
Jul 27, 2021·Environmental Science and Pollution Research International·Nasreddine El OmariAbdelhakim Bouyahya

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR

Software Mentioned

FlowJo
GraphPad Prism

Related Concepts

Related Feeds

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.