The NAD Metabolome--a Key Determinant of Cancer Cell Biology

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2012 Sep 29

PMID 23018234

Citations 298

Authors

Alberto Chiarugi

Christian Dolle

Roberta Felici

Mathias Ziegler

Affiliations

Soon will be listed here.

Abstract

NAD is a vital molecule in all organisms. It is a key component of both energy and signal transduction--processes that undergo crucial changes in cancer cells. NAD(+)-dependent signalling pathways are many and varied, and they regulate fundamental events such as transcription, DNA repair, cell cycle progression, apoptosis and metabolism. Many of these processes have been linked to cancer development. Given that NAD(+)-dependent signalling reactions involve the degradation of the molecule, permanent nucleotide resynthesis through different biosynthetic pathways is crucial for incessant cancer cell proliferation. This necessity supports the targeting of NAD metabolism as a new therapeutic concept for cancer treatment.

Citing Articles

Spectroscopic Study of Methylene Blue Interaction with Coenzymes and its Effect on Tumor Metabolism.

Pominova D, Ryabova A, Skobeltsin A, Markova I, Romanishkin I Sovrem Tekhnologii Med. 2025; 17(1):18-25.

PMID: 40071073 PMC: 11892571. DOI: 10.17691/stm2025.17.1.02.

NAD+ Suppresses EV-D68 Infection by Enhancing Anti-Viral Effect of SIRT1.

Wang Y, Li H, Huang X, Huang Y, Lv M, Tang H Viruses. 2025; 17(2).

PMID: 40006932 PMC: 11860866. DOI: 10.3390/v17020175.

Redox state of NAD modulates the activation of Na-bicarbonate cotransporter NBCe1-B via IRBIT and L-IRBIT.

Gui T, Liu Y, Fu M, Wu H, Su P, Feng X Sci China Life Sci. 2025; .

PMID: 39985648 DOI: 10.1007/s11427-024-2750-0.

Autophagy induced by metabolic processes leads to solid tumor cell metastatic dormancy and recurrence.

Ferdousmakan S, Mansourian D, Seyedi Asl F, Fathi Z, Maleki-Sheikhabadi F, Nabi Afjadi M Med Oncol. 2025; 42(3):62.

PMID: 39899220 DOI: 10.1007/s12032-025-02607-6.

Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer.

Visal T, Bayraktar R, den Hollander P, Attathikhun M, Zhou T, Wang J Cancer Res. 2025; 85(5):894-911.

PMID: 39853244 PMC: 11873730. DOI: 10.1158/0008-5472.CAN-24-0400.

References

Meszaros L, Bak J, Chu A . Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel. Nature. 1993; 364(6432):76-9. DOI: 10.1038/364076a0. View

Tong L, Denu J . Function and metabolism of sirtuin metabolite O-acetyl-ADP-ribose. Biochim Biophys Acta. 2010; 1804(8):1617-25. PMC: 3310390. DOI: 10.1016/j.bbapap.2010.02.007. View

Lukasova M, Hanson J, Tunaru S, Offermanns S . Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potentials. Trends Pharmacol Sci. 2011; 32(12):700-7. DOI: 10.1016/j.tips.2011.08.002. View

Rouleau M, Patel A, Hendzel M, Kaufmann S, Poirier G . PARP inhibition: PARP1 and beyond. Nat Rev Cancer. 2010; 10(4):293-301. PMC: 2910902. DOI: 10.1038/nrc2812. View

Von Heideman A, Berglund A, Larsson R, Nygren P . Safety and efficacy of NAD depleting cancer drugs: results of a phase I clinical trial of CHS 828 and overview of published data. Cancer Chemother Pharmacol. 2009; 65(6):1165-72. DOI: 10.1007/s00280-009-1125-3. View

Papeo G, Forte B, Orsini P, Perrera C, Posteri H, Scolaro A . Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to maturity?. Expert Opin Ther Pat. 2009; 19(10):1377-400. DOI: 10.1517/13543770903215883. View

Hallows W, Lee S, Denu J . Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci U S A. 2006; 103(27):10230-10235. PMC: 1480596. DOI: 10.1073/pnas.0604392103. View

Calvert H, Azzariti A . The clinical development of inhibitors of poly(ADP-ribose) polymerase. Ann Oncol. 2011; 22 Suppl 1:i53-9. DOI: 10.1093/annonc/mdq667. View

Kim J, Chen J, Lou Z . DBC1 is a negative regulator of SIRT1. Nature. 2008; 451(7178):583-6. DOI: 10.1038/nature06500. View

10.

Balo-Banga J, Weber G . Increased 5-phospho-alpha-D-ribose-1-diphosphate synthetase (ribosephosphate pyrophosphokinase, EC 2.7.6.1) activity in rat hepatomas. Cancer Res. 1984; 44(11):5004-9. View

11.

Beauparlant P, Bedard D, Bernier C, Chan H, Gilbert K, Goulet D . Preclinical development of the nicotinamide phosphoribosyl transferase inhibitor prodrug GMX1777. Anticancer Drugs. 2009; 20(5):346-54. DOI: 10.1097/CAD.0b013e3283287c20. View

12.

Ravaud A, Cerny T, Terret C, Wanders J, Bui B, Hess D . Phase I study and pharmacokinetic of CHS-828, a guanidino-containing compound, administered orally as a single dose every 3 weeks in solid tumours: an ECSG/EORTC study. Eur J Cancer. 2005; 41(5):702-7. DOI: 10.1016/j.ejca.2004.12.023. View

13.

Schreiber V, Dantzer F, Ame J, de Murcia G . Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol. 2006; 7(7):517-28. DOI: 10.1038/nrm1963. View

14.

Mangerich A, Burkle A . How to kill tumor cells with inhibitors of poly(ADP-ribosyl)ation. Int J Cancer. 2010; 128(2):251-65. DOI: 10.1002/ijc.25683. View

15.

Alano C, Swanson R . Players in the PARP-1 cell-death pathway: JNK1 joins the cast. Trends Biochem Sci. 2006; 31(6):309-11. DOI: 10.1016/j.tibs.2006.04.006. View

16.

Barber M, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z . SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012; 487(7405):114-8. PMC: 3412143. DOI: 10.1038/nature11043. View

17.

Helleday T . The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol. 2011; 5(4):387-93. PMC: 5528309. DOI: 10.1016/j.molonc.2011.07.001. View

18.

Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J . The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One. 2008; 3(4):e2020. PMC: 2289879. DOI: 10.1371/journal.pone.0002020. View

19.

Smith J, Brachmann C, Celic I, Kenna M, Muhammad S, Starai V . A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci U S A. 2000; 97(12):6658-63. PMC: 18692. DOI: 10.1073/pnas.97.12.6658. View

20.

Wang R, Sengupta K, Li C, Kim H, Cao L, Xiao C . Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008; 14(4):312-23. PMC: 2643030. DOI: 10.1016/j.ccr.2008.09.001. View