Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2016 Volume 14 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2016 Volume 14 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites

  • Authors:
    • Guoqiang Ai
    • Rakesh Dachineni
    • D. Ramesh Kumar
    • Lloyd F. Alfonso
    • Srinivasan Marimuthu
    • G. Jayarama Bhat
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Sciences, South Dakota State University College of Pharmacy, Avera Health and Sciences Center, Brookings, SD 57007, USA, D'Youville College School of Pharmacy, Buffalo, NY 14201, USA
  • Pages: 1726-1732
    |
    Published online on: June 27, 2016
       https://doi.org/10.3892/mmr.2016.5449
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT‑29 colorectal cancer cells, in order to compare aspirin‑mediated acetylation of G6PD and its activity between HCT 116 and HT‑29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT‑29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin‑acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Kaiser J: Will an aspirin a day keep cancer away? Science. 337:1471–1473. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Thun MJ, Jacobs EJ and Patrono C: The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 9:259–267. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Chan AT, Arber N, Burn J, Chia WK, Elwood P, Hull MA, Logan RF, Rothwell PM, Schrör K and Baron JA: Aspirin in the chemoprevention of colorectal neoplasia: An overview. Cancer Prev Res (Phila). 5:164–178. 2012. View Article : Google Scholar

4 

Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, Lee R, Belch JF, Wilson M, Mehta Z and Meade TW: Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: Analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 379:1602–1612. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Ferrández A, Piazuelo E and Castells A: Aspirin and the prevention of colorectal cancer. Best Pract Res Clin Gastroenterol. 26:185–195. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Alfonso L, Ai G, Spitale RC and Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 111:61–67. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Dovizio M, Bruno A, Tacconelli S and Patrignani P: Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res. 191:39–65. 2013. View Article : Google Scholar

8 

Kopp E and Ghosh S: Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 265:956–959. 1994. View Article : Google Scholar : PubMed/NCBI

9 

Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, et al: The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 336:918–922. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Choi HW, Tian M, Song F, Venereau E, Preti A, Park SW, Hamilton K, Swapna GV, Manohar M, Moreau M, et al: Aspirin's active metabolite salicylic acid targets high mobility group Box 1 to modulate inflammatory responses. Mol Med. 21:526–535. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Dachineni R, Ai G, Kumar DR, Sadhu SS, Tummala H and Bhat GJ: Cyclin A2 and CDK2 as novel targets of aspirin and salicylic acid: A potential role in cancer prevention. Mol Cancer Res. 14:241–252. 2016. View Article : Google Scholar

12 

Alfonso LF, Srivenugopal KS and Bhat GJ: Does aspirin acetylate multiple cellular proteins? (Review). Mol Med Rep. 2:533–537. 2009.PubMed/NCBI

13 

Marimuthu S, Chivukula RS, Alfonso LF, Moridani M, Hagen FK and Bhat GJ: Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets. Int J Oncol. 39:1273–1283. 2011.PubMed/NCBI

14 

Bateman LA, Zaro BW, Miller SM and Pratt MR: An alkyne-aspirin chemical reporter for the detection of aspirin-dependent protein modification in living cells. J Am Chem Soc. 135:14568–14573. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Wang J, Zhang CJ, Zhang J, He Y, Lee YM, Chen S, Lim TK, Ng S, Shen HM and Lin Q: Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP). Sci Rep. 5:78962015. View Article : Google Scholar : PubMed/NCBI

16 

Alfonso LF, Srivenugopal KS, Arumugam TV, Abbruscato TJ, Weidanz JA and Bhat GJ: Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells. Int J Oncol. 34:597–608. 2009.PubMed/NCBI

17 

Ai G, Dachineni R, Kumar DR, Marimuthu S, Alfonso LF and Bhat GJ: Aspirin acetylates wild type and mutant p53 in colon cancer cells: Identification of aspirin acetylated sites on recombinant p53. Tumor Biol. Nov 23–2015.Epub ahead of print.

18 

Stanton RC: Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life. 64:362–369. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Furuta E, Okuda H, Kobayashi A and Watabe K: Metabolic genes in cancer: Their roles in tumor progression and clinical implications. Biochim Biophys Acta. 1805:141–152. 2010.PubMed/NCBI

20 

Kanno H, Kondoh T and Yoshida A: 5′ Structure and expression of human glucose-6-phosphate dehydrogenase mRNA. DNA Cell Biol. 12:209–215. 1993. View Article : Google Scholar : PubMed/NCBI

21 

Bautista JM, Mason PJ and Luzzatto L: Human glucose-6-phosphate dehydrogenase. Lysine 205 is dispensable for substrate binding but essential for catalysis. FEBS Lett. 366:61–64. 1995. View Article : Google Scholar : PubMed/NCBI

22 

Karplus K: SAM-T08, HMM-based protein structure prediction. Nucleic Acids Res. 37:W492–W497. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Pinckard RN, Hawkins D and Farr RS: In vitro acetylation of plasma proteins, enzymes and DNA by aspirin. Nature. 219:68–69. 1968. View Article : Google Scholar : PubMed/NCBI

24 

Marchler-Bauer A, Derbyshire MK, Gonzales NR, Lu S, Chitsaz F, Geer LY, Geer RC, He J, Gwadz M, Hurwitz DI, et al: CDD: NCBI's conserved domain database. Nucleic Acids Res. 43(Database Issue): D222–D226. 2015. View Article : Google Scholar

25 

Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, et al: Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 33:1304–1320. 2014.PubMed/NCBI

26 

Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV and Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 325:834–840. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Au SW, Gover S, Lam VM and Adams MJ: Human glucose-6-phosphate dehydrogenase: The crystal structure reveals a structural NADP (+) molecule and provides insights into enzyme deficiency. Structure. 8:293–303. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Jeffery J, Hobbs L and Jöernvall H: Glucose 6-phosphate dehydrogenase from Saccharomyces cerevisiae: Characterization of a reactive lysine residue labeled with acetylsalicylic acid. Biochemistry. 24:666–671. 1985. View Article : Google Scholar : PubMed/NCBI

29 

Tsouko E, Khan AS, White MA, Han JJ, Shi Y, Merchant FA, Sharpe MA, Xin L and Frigo DE: Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated mechanism and its role in prostate cancer cell growth. Oncogenesis. 3:e1032014. View Article : Google Scholar : PubMed/NCBI

30 

Wang J, Yuan W and Chen Z, Wu S, Chen J, Ge J, Hou F and Chen Z: Overexpression of G6PD is associated with poor clinical outcome in gastric cancer. Tumour Biol. 33:95–101. 2012. View Article : Google Scholar

31 

Du W, Jiang P, Mancuso A, Stonestrom A, Brewer MD, Minn AJ, Mak TW, Wu M and Yang X: TAp73 enhances the pentose phosphate pathway and supports cell proliferation. Nat Cell Biol. 15:991–1000. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Baba M, Yamamoto R, Iishi H, Tatsuta M and Wada A: Role of glucose-6-phosphate dehydrogenase on enhanced proliferation of pre-neoplastic and neoplastic cells in rat liver induced by N-nitrosomorpholine. Int J Cancer. 43:892–895. 1989. View Article : Google Scholar : PubMed/NCBI

33 

Kuo W, Lin J and Tang TK: Human glucose-6-phosphate dehydrogenase (G6PD) gene transforms NIH 3T3 cells and induces tumors in nude mice. Int J Cancer. 85:857–864. 2000. View Article : Google Scholar : PubMed/NCBI

34 

Kuo WY and Tang TK: Effects of G6PD overexpression in NIH3T3 cells treated with tert-butyl hydroperoxide or paraquat. Free Radic Biol Med. 24:1130–1138. 1998. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ai G, Dachineni R, Kumar D, Alfonso LF, Marimuthu S and Bhat G: Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites. Mol Med Rep 14: 1726-1732, 2016.
APA
Ai, G., Dachineni, R., Kumar, D., Alfonso, L.F., Marimuthu, S., & Bhat, G. (2016). Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites. Molecular Medicine Reports, 14, 1726-1732. https://doi.org/10.3892/mmr.2016.5449
MLA
Ai, G., Dachineni, R., Kumar, D., Alfonso, L. F., Marimuthu, S., Bhat, G."Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites". Molecular Medicine Reports 14.2 (2016): 1726-1732.
Chicago
Ai, G., Dachineni, R., Kumar, D., Alfonso, L. F., Marimuthu, S., Bhat, G."Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites". Molecular Medicine Reports 14, no. 2 (2016): 1726-1732. https://doi.org/10.3892/mmr.2016.5449
Copy and paste a formatted citation
x
Spandidos Publications style
Ai G, Dachineni R, Kumar D, Alfonso LF, Marimuthu S and Bhat G: Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites. Mol Med Rep 14: 1726-1732, 2016.
APA
Ai, G., Dachineni, R., Kumar, D., Alfonso, L.F., Marimuthu, S., & Bhat, G. (2016). Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites. Molecular Medicine Reports, 14, 1726-1732. https://doi.org/10.3892/mmr.2016.5449
MLA
Ai, G., Dachineni, R., Kumar, D., Alfonso, L. F., Marimuthu, S., Bhat, G."Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites". Molecular Medicine Reports 14.2 (2016): 1726-1732.
Chicago
Ai, G., Dachineni, R., Kumar, D., Alfonso, L. F., Marimuthu, S., Bhat, G."Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites". Molecular Medicine Reports 14, no. 2 (2016): 1726-1732. https://doi.org/10.3892/mmr.2016.5449
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team