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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
December-2016 Volume 12 Issue 6

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
December-2016 Volume 12 Issue 6

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

Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms

  • Authors:
    • Xiao Deng
    • Qianghong Pu
    • Erhao Wang
    • Chao Yu
  • View Affiliations / Copyright

    Affiliations: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, P.R. China
  • Pages: 5309-5314
    |
    Published online on: October 25, 2016
       https://doi.org/10.3892/ol.2016.5317
  • 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

Human cytochrome P450 (CYP) 2A6 participates in the metabolism of nicotine and precarcinogens, thus the deliberate inhibition of CYP2A6 may reduce cigarette consumption and therefore reduce the risk of developing the types of cancer associated with smoking. The inhibitory effects and mechanisms of celery (Apium graveolens) extract on mouse CYP2A5 and human CYP2A6 activity remain unclear. These effects were investigated in mouse and human liver microsomes using coumarin 7‑hydroxylation in a probe reaction. Celery extract reduced CYP2A5 and CYP2A6 activities in vitro in a dose‑dependent manner. In vivo experiments also showed that celery extract markedly decreased CYP2A5 activity. The inhibition of celery extract on CYP2A5 was time‑ and nicotinamide adenine dinucleotide phosphate (NADPH)‑independent, and was markedly reduced by ultracentrifugation. Additionally, the inhibition of celery extract on CYP2A6 was time and NADPH‑dependent. Levels of inhibition were characterized by a Ki, the measure of the tightness of bonds between the enzyme and its inhibitor, of 266.4 µg/ml for CYP2A5, and a Ki of 1,018 µg/ml and Kinact of 0.3/min for CYP2A6. Kinact is the maximal rate of enzyme inactivation at a saturating concentration of inhibitor. The coumarin derivative 5‑methoxypsoralen present in celery extract did not solely to the inhibition of CYP2A5/6 activity. In conclusion, celery extract inhibited the levels of mouse CYP2A5 and human CYP2A6 activity via different mechanisms: Mixed competitive inhibition for CYP2A5 and mechanism‑based inhibition for CYP2A6.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Raunio H and Rahnasto-Rilla M: CYP2A6: Genetics, structure, regulation, and function. Drug Metabol Drug Interact. 27:73–88. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Raunio H, Rautio A and Pelkonen O: The CYP2A subfamily: Function, expression and genetic polymorphism. IARC Sci Publ. 148:197–207. 1999.

3 

Pelkonen P, Lang MA, Wild CP, Negishi M and Juvonen RO: Activation of aflatoxin B1 by mouse CYP2A enzymes and cytotoxicity in recombinant yeast cells. Eur J Pharmacol. 292:67–73. 1994.PubMed/NCBI

4 

Camus AM, Geneste O, Honkakoski P, Béréziat JC, Henderson CJ, Wolf CR, Bartsch H and Lang MA: High variability of nitrosamine metabolism among individuals: Role of cytochromes P450 2A6 and 2E1 in the dealkylation of N-nitrosodimethylamine and N-nitrosodiethylamine in mice and humans. Mol Carcinog. 7:268–275. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Oscarson M: Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: Implications for interindividual differences in nicotine metabolism. Drug Metab Dispos. 29:91–95. 2001.PubMed/NCBI

6 

Tyndale RF and Sellers EM: Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk. Drug Metab Dispos. 29:548–552. 2001.PubMed/NCBI

7 

Miyamoto M, Umetsu Y, Dosaka-Akita H, Sawamura Y, Yokota J, Kunitoh H, Nemoto N, Sato K, Ariyoshi N and Kamataki T: CYP2A6 gene deletion reduces susceptibility to lung cancer. Biochem Biophys Res Commun. 261:658–660. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Sowbhagya HB: Chemistry, technology, and nutraceutical functions of celery (Apium graveolens L.): An overview. Crit Rev Food Sci Nutr. 54:389–398. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Madkour NK: Beneficial role of celery oil in lowering the di(2-ethylhexyl) phthalate-induced testicular damage. Toxicol Ind Health. 30:861–872. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Jakovljevic V, Raskovic A, Popovic M and Sabo J: The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism. Eur J Drug Metab Pharmacokinet. 27:153–156. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. Biol Chem. 193:265–274. 1951.

12 

Pinto LF, Moraes E, Albano RM, Silva MC, Godoy W, Glisovic T and Lang MA: Rat oesophageal cytochrome P450 (CYP) monooxygenase system: Comparison to the liver and relevance in N-nitrosodiethylamine carcinogenesis. Carcinogenesis. 22:1877–1883. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265–275. 1951.PubMed/NCBI

14 

Aitio A: A simple and sensitive assay of 7-ethoxycoumarin deethylation. Anal Biochem. 85:488–491. 1978. View Article : Google Scholar : PubMed/NCBI

15 

Farooq S, Shakeel-u-Rehman, Dangroo NA, Priya D, Banday JA, Sangwan PL, Qurishi MA, Koul S and Saxena AK: Isolation, cytotoxicity evaluation and HPLC-quantification of the chemical constituents from Prangos pabularia. PLoS One. 9:e1087132014. View Article : Google Scholar : PubMed/NCBI

16 

Perloff ES, Mason AK, Dehal SS, Blanchard AP, Morgan L, Ho T, Dandeneau A, Crocker RM, Chandler CM, Boily N, et al: Validation of cytochrome P450 time-dependent inhibition assays: A two-time point IC50 shift approach facilitates kinact assay design. Xenobiotica. 39:99–112. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Lee JY, Lee SY, Oh SJ, Lee KH, Jung YS and Kim SK: Assessment of drug-drug interactions caused by metabolism-dependent cytochrome P450 inhibition. Chem Biol Interact. 198:49–56. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Mäenpää J, Sigusch H, Raunio H, Syngelmä T, Vuorela P, Vuorela H and Pelkonen O: Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes. Biochem Pharmacol. 45:1035–1042. 1993. View Article : Google Scholar : PubMed/NCBI

19 

Juvonen RO, Gynther J, Pasanen M, Alhava E and Poso A: Pronounced differences in inhibition potency of lactone and non-lactone compounds for mouse and human coumarin 7-hydroxylases (CYP2A5 and CYP2A6). Xenobiotica. 30:81–92. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Wood AW: Genetic regulation of coumarin hydroxylase activity in mice. Biochemical characterization of the enzyme from two inbred strains and their F1 hybrid. J Biol Chem. 254:5641–5646. 1979.PubMed/NCBI

21 

Rahnasto M, Raunio H, Poso A and Juvonen RO: More potent inhibition of human CYP2A6 than mouse CYP2A5 enzyme activities by derivatives of phenylethylamine and benzaldehyde. Xenobiotica. 33:529–539. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Lindberg RL and Negishi M: Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue. Nature. 339:632–634. 1989. View Article : Google Scholar : PubMed/NCBI

23 

Negishi M, Iwasaki M, Juvonen RO and Aida K: Alteration of the substrate specificity of mouse 2A P450s by the identity of residue-209: Steroid-binding site and orientation. J Steroid Biochem Mol Biol. 43:1031–1036. 1992. View Article : Google Scholar : PubMed/NCBI

24 

Visoni S, Meireles N, Monteiro L, Rossini A and Pinto LF: Different modes of inhibition of mouse Cyp2a5 and rat CYP2A3 by the food-derived 8-methoxypsoralen. Food Chem Toxicol. 46:1190–1195. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Draper AJ, Madan A and Parkinson A: Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch Biochem Biophys. 341:47–61. 1997. View Article : Google Scholar : PubMed/NCBI

26 

von Weymarn LB, Zhang QY, Ding X and Hollenberg PF: Effects of 8-methoxypsoralen on cytochrome P450 2A13. Carcinogenesis. 26:621–629. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Liu YL, Xu Y, Li F, Chen H and Guo SL: CYP2A6 deletion polymorphism is associated with decreased susceptibility of lung cancer in Asian smokers: A meta-analysis. Tumour Biol. 34:2651–2657. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Mwenifumbo JC and Tyndale RF: Genetic variability in CYP2A6 and the pharmacokinetics of nicotine. Pharmacogenomics. 8:1385–1402. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Nakajima M: Smoking behavior and related cancers: The role of CYP2A6 polymorphisms. Curr Opin Mol Ther. 9:538–544. 2007.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Deng X, Pu Q, Wang E and Yu C: Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms. Oncol Lett 12: 5309-5314, 2016.
APA
Deng, X., Pu, Q., Wang, E., & Yu, C. (2016). Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms. Oncology Letters, 12, 5309-5314. https://doi.org/10.3892/ol.2016.5317
MLA
Deng, X., Pu, Q., Wang, E., Yu, C."Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms". Oncology Letters 12.6 (2016): 5309-5314.
Chicago
Deng, X., Pu, Q., Wang, E., Yu, C."Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms". Oncology Letters 12, no. 6 (2016): 5309-5314. https://doi.org/10.3892/ol.2016.5317
Copy and paste a formatted citation
x
Spandidos Publications style
Deng X, Pu Q, Wang E and Yu C: Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms. Oncol Lett 12: 5309-5314, 2016.
APA
Deng, X., Pu, Q., Wang, E., & Yu, C. (2016). Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms. Oncology Letters, 12, 5309-5314. https://doi.org/10.3892/ol.2016.5317
MLA
Deng, X., Pu, Q., Wang, E., Yu, C."Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms". Oncology Letters 12.6 (2016): 5309-5314.
Chicago
Deng, X., Pu, Q., Wang, E., Yu, C."Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms". Oncology Letters 12, no. 6 (2016): 5309-5314. https://doi.org/10.3892/ol.2016.5317
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