The tumour thiolome as a potential target for anticancer drug development - time for a re-valuation of this area of cancer research.

Main Article Content

Michael Gronow, PhD (Cantab)

Abstract

This review is concerned with the role of various thiol constituents of the eukaryote cellular thiolome, particularly the part they play in the metabolism of tumour cells. The thiolome can be divided into two sections of high and low molecular weight thiol moieties and these are discussed. The impact of the discovery of high concentrations of a new unknown low molecular weight thiol in a tumour thiolome is also discussed. Its presence may have important ramifications in the search for new and more effective chemotherapeutic drugs to treat metastatic tumour cell growths.

Keywords: tumour, cancer, anticancer drug development, cancer research, review article

Article Details

How to Cite
GRONOW, Michael. The tumour thiolome as a potential target for anticancer drug development - time for a re-valuation of this area of cancer research.. Medical Research Archives, [S.l.], v. 12, n. 1, jan. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5038>. Date accessed: 03 mar. 2024. doi: https://doi.org/10.18103/mra.v12i1.5038.
Section
Review Articles

References

1. Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh,H, Leonart,M.E.L. Oxidative stress and Cancer: an overview, Ageing Res. Rev.2012;12(1):376-90. doi: 10.1016/j.arr.2012.10.004

2. Paschos A, Pandya R, Duivenvoorden WCM. Pinthus JH. Oxidative Stress in Prostate Cancer : Changing Research Concepts Towards a Novel Paradigm for Prevention and Therapeutics Prostate Cancer Prostatic Dis. 2013;16(3):217-225. doi:10.1038/pcan.2013.13

3. Hayes JD, Albena T, Dinkova-Kostova,Tew KD. Oxidative Stress in Cancer. Review in Cancer Cell. 2020;38(2):167-197. doi: 10.1016/j.ccell.2020.06.001

4. Domenico C.Marengo, B. "Paradox Role of Oxidative Stress in Cancer: State of the Art". Antioxidants. 2022; 11(5): 1027. doi.org/10.3390/antiox11051027

5. Guzman Barron,ES. Thiol groups of biological importance, Advances in Enxymology, 1957;11 201-265. doi: 10.1002/9780470122563.ch4

6. Fahey RC, Hunt J.S.Windham,G.C. On the Cysteine and Cystine Content of Proteins, J.Mol.Evol. 1977; 10: 155-160. doi: 10.1007/BF01751808.

7. Go,Y-M, Joshua D Chandler JD Jones DP. The cysteine proteome Free radical biology and Medicine 2015; 84: 227-245. doi.org/10.1016/j.freeradbiomed.2015.03.022

8. Poole LB. The basics of thiols and cysteines in redox biology and chemistry. Free Radical Biology and Medicine. 2015; 80: 148–157. doi: 10.1016/j.freeradbiomed.2014.11.013.

9. Wu S,.Huizhe HL,Wang, Zhao HW, Hu Q, Yang Y. Cysteinome: The first comprehensive database for proteins with targetable cysteine and their covalent inhibitors. 2016; PMID: 275532 doi: 10.1016/j.bbrc.2016.08.109

10. Orme-Johnson WH. Iron-sulfur Proteins: Structure and Function. Annu Rev Biochem. 1973;42(0):159-204. doi: 10.1146/annurev.bi.42.070173.001111.

11. Rouault TA. Mammalian iron-sulphur proteins: novel insights into biogenesis and function. Nat Rev Mol Cell Biol. 2015;16(1):45-55. doi:10.1038/nrm3909

12. Daher B,Vuceti M, Pouysségur J. Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death. Front. Oncol. 2020;10 10:723. doi: 10.3389/fonc.2020.00723

13. James,J.,Gideon,A.M.,Roy,D., and Mandal,A. Iron Sulfur Clusters and ROS in Cancer. Handbook of Oxidative Stress in Cancer: Mechanistic Aspects In: Chakraborti, S., Ray, B.K., Roychoudhury, S. (eds). 2022; 291–306 Springer, Singapore. https://doi.org/10.1007/978-981-15-9411-3_24

14. Zhang,M., Liu Z, Le Y, Gu Z, Zhao H. Review: Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer, Oxidative Medicine and Cellular Longevity. 2022, Article ID 7449941, 15 pages. https://doi.org/10.1155/2022/7449941

15. Ye Q, Lui J, Xei K. Zinc finger proteins and regulation of the hallmarks of cancer histology and histopathology.2019; 34(10):1097-1109 doi:10.14670/HH-18-121

16. Lincoln DT, Ali Emadi EM,Tonissen,KF. Clarke FM. The thioredoxin–thioredoxin reductase system: over-expression in human cancer, Anticancer Res. 2003;23: 2425–2433

17. Reuter SC, Gupta MM, Chaturvedi BB, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic. Biol. Med. 2010;49(11): 1603-1616.
doi: 10.1016/j.freeradbiomed.2010.09.006

18. Harris IS, Treloar AE, Inoue S ”et al”. Glutathione and Thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell.2015; 27: 211-222; doi.org/10.1016/j.ccell.2014.11.019

19. Bhatia M,McGrath KL,TrapaniGD, Charoentong P, Shah F, King MM Clarke FM Tonissen KF. The thioredoxin system in breast cancer cell invasion and migration. Redox Biology.2016; 8: 68-78. doi.org/10.1016/j.redox.2015.12.004

20. Hopkins BL, Hopkins C, Neumann CL. Redoxins as gatekeepers of the transcriptional oxidative stress response. Redox Biology. 2019; 21(12):101104. doi: 10.1016/j.redox.2019.101104

21. Karlenius TC, Tonissen KF. Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor Oxygenation. Cancers 2010; 2: 209-232; doi:10.3390/cancers2020209

22. Ghareeb H, Metanis M. Review: The Thioredoxin System: A Promising Target for Cancer Drug Development. Chemistry – A European Journal. 2020; 26(45):10175-10184 doi: 10.1002/chem.201905792

23. Deng J, Pan T, Liu Z. et al. The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control. British Journal of Cancer. 2023; https://doi.org/10.1038/s41416-023-02442-4

24. Hayes J, Pulford D. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol1995;30(6):445-600. DOI:10.3109/10409239509083491

25. Hong W, SNAREs and traffic- a review. Biochim. Biophys. Acta.2005;1744(2):120-44 doi: 10.1016/j.bbamcr.2005.03.014.

26. Meng J,Wang J. Role of SNARE proteins in tumourigenesis and their potential as targets for novel anti-cancer therapeutics – a review; Biochim Biophys Acta. 2015;1856(1): 1-12 doi: 10.1016/j.bbcan.2015.04.002. Epub 2015 May 5. PMID: 25956199.

27. Meister A, Anderson M. Glutathione. Ann Rev Biochem. 1963;52: 711-760 doi:10.1146/annurev.bi.52.070183.003431 10.1146/annurev.bi.52.070183.003431

28. Childs S. Haroune N, Williams L, Gronow M. Investigation of the Low Molecular Weight Thiol Composition in a Metastatic Prostate Cancer Cell Line (LNCaP) by LC-UV-MS and NMR after labelling with the Ellman Reagent. American Journal of Analytical Chemistry, 2018; 8: 1-18. doi.org/10.4236/ajac.2017.81001

29. Giles GI. The redox regulation of thiol dependent signaling pathways in cancer. Curr Pharm Des. 2006; 12:4427–4443. doi: 10.2174/138161206779010549

30. Acharyah A. Das I. Chandhok D. and SahaT., Redox regulation in cancer. A double-edged sword with therapeutic potential Oxidative Medicine and Cellular Longevity, 2010; 3:1 23-34. doi: 10.4161/oxim.3.1.10095

31. Castaldo SA Freitas JR Conchinha NV Madureira PA. Oxid Med Cell Longev. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems.016;2016:8413032. (2016); doi: 10.1155/2016/8413032.

32. Revesz L, Edgren M.R, Wainson,AA. Selective toxicity of buthionine sulfoximine (BSO) in melanoma cells in vitro and in vivo Int.J.Radiat.Oncol.Biol.Phys., 1994;29: 403-406. doi: 10.1016/0360-3016(94)90298-4.

33. Arrick B.A. Nathan,C.F.and Cohn,Z.A., Inhibition of Glutathione synthesis augments lysis of murine tumour cells by sulfhydryl-reactive antineoplastics, J.Clin.Invest.1983; 77: 258-267; doi: 10.1172/jci110766

34. Balendiran GK Dabur R, Fraser D. "The role of glutathione in cancer". Cell Biochemistry and Function. 2004; 22 (6): 343– 352. doi:10.1002/cbf.1149. PMID 15386533. S2CID 26950450

35. Estrela J.M, Ortega,A. Obrador E. Glutathione in Cancer Biology and Therapy Crit Rev Clin Lab Sci. 2006; 43(2):143-181. doi: 10.1080/10408360500523878

36. Traverso N, Ricciarelli,R, Nitti M, Marengo B, Furfaro AL, Pronzato MA, Marinari UM, Domenicotti C. Role of glutathione in cancer progression and chemoresistance.,Oxid Med Cell Longev. 2013; 2013: 972913. doi: 10.1155/2013/972913

37. Bansal A. and Celeste SM Glutathione metabolism in cancer progression and treatment resistance, J. Cell Biol. 2018; 217(7): 2291–2298; doi.org/10.1083/jcb.201804161

38. Kennedy L, Sandhu,JK., Harper,M-E, Cuperlovic-Culf,M. Role of Glutathione in Cancer: From Mechanisms to Therapies. Biomolecules. 2020; 10(10): 1429; doi: 10.3390/biom10101429.

39. Connors TA. Protection against the toxicity of alkylating agents by thiols: the mechanism of protection and its relevance to cancer chemotherapy a review Eur.J.Cancer. 1966; 2: 293-305; doi.org/10.1016/0014-2964(66)90042-9

40. Gronow M. Studies on the thiol components of isolated nuclei. Journal of Analytical Sciences, Methods and Instrumentation.2020;10:36-42. doi.org/10.4236/jasmi.2020.101003

41. Gronow M, Lewis FA, Thiols attached to rat liver non-histone nuclear proteins. Exptl. Cell. Res., 1975; 93: 225-229. doi.org/10.1016/0014-4827(75)90443-7

42. Gronow M. Cellular protein thiols: studies on human prostate cell lines; a lymph node cancer line (LNCaP) and a virally transformed normal cell line (PNT2). Oncol.Res.Rev. 2018;1(3):1-6. doi.10.15761/ORR.1000116

43. Gronow M. Isolation and analysis of a non-protein low molecular weight thiol-mercurial adduct from human prostate lymph node cells (LNCaP) Bioscience Rep. 2020a; 40 (6):1-6 BSR20201343. doi.org/10.1042/BSR20201343

44. Gronow M. Further Analytical Studies on a Mercuri Thiol Adduct Isolated from a Human Prostate Cancer Cell Line (LNCaP) Journal of Analytical Sciences, Methods and Instrumentation. 2022b; 12, 31-47; doi: 10.4236/jasmi.2022.123003

45. Gronow M. Studies on the Composition of The Low Molecular Weight Thiols Present in Tumour Cells– Is There "An Elephant in The Room”? An Autobiographical Review. Cancer Science & Research.2022a; 5(2): 1-13. doi:10.33425/2639-8478.1088

46. Brancaccio M,Tangherlini M. Danovaro R and Castellano I. Metabolic Adaptations to Marine Environments: Molecular Diversity and Evolution of Ovothiol Biosynthesis in Bacteria. Genome Biology and Evolution.2021;13((9): 1-15 https://doi.org/10.1093/gbe/evab169

47. Halliwell B, Cheah I. Ergothioneine, where are we now? FEBS Letters. 2022;596:1227–1230. https://doi.org/10.1002/1873-3468.14350

48. Mock M, Edavettal S, Langmead C,Russell A. AI can help to speed up drug discovery - but only if we give it the right data. Nature. 2023; 621: 467-470 (2023) PMID: 37726439. doi: 10.1038/d41586-023-02896-9