Skip to main content
SpringerLink
Log in

Oral supplementation of piperine leads to altered phase II enzymes and reduced DNA damage and DNA-protein cross links in Benzo(a)pyrene induced experimental lung carcinogenesis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

In recent years, considerable emphasis has been focused on identifying new chemopreventive agents, which could be useful for the human population. Piperine is a pure, pungent alkaloid constituent of black and long peppers (piper nigrum and piper longum), which is a most common spice used throughout the world. In the present study, we examined the protective role of piperine during experimental lung carcinogenesis with reference to its effect on DNA damage and detoxification enzyme system. The activities of detoxifying enzymes such as glutathione transferase (GST), quinone reductase (QR) and UDP-glucuronosyl transferase (UDP-GT) were found to be decreased while the hydrogen peroxide level was increased in the lung cancer bearing animals. Supplementation of piperine (50 mg/kg bwt) enhanced the detoxification enzymes and reduced DNA damage as determined by single cell electrophoresis. Furthermore, the DNA-Protein cross links which was found to be high in lung cancer bearing animals was also modulated upon supplementation with piperine. Our present results explain the understanding of unique association between anti-peroxidative effect of piperine and ultimately the capability of piperine to prevent cancer. (Mol Cell Biochem 268: 141–147, 2005)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hans peter W, Deuter M, Imilda E: Chemoprevention of tobacco smoke nduced lung carcinogenesis in Mice. Carcinogenesis 21: 977–982, 2000

    Article  Google Scholar 

  2. Eiserich JP, Van der vliet A, Haldeman GJ, Hallowell B, Cross CE: Dietary antioxidants and cigarette smoke induced bimolecular damage. Am J Clim Nutr 62: 1490s–1500s, 1995

    Google Scholar 

  3. Witschi H, Uyeminami D, Moran D, Espiritu I: Chemoprevention of tobacco-smoke lung carcinogenesis in mice after cessation of smoke exposure. Carcinogensis. 21: 977–982, 2000

    Article  Google Scholar 

  4. Pool BL, Bub A, Muller H, Wollowski I, Rechkemmet G: Consumption of vegetables reduces genetic damage in humans. Carcinogenesis 18: 1847–1850, 1997

    Article  Google Scholar 

  5. Thirunavukkarasu C, Sakthisekaran D: Sodium selenite, dietary Micronutrient, prevents the lymphocyte DNA damage induced by N-Nitrosodiethylamine and phenobarbital promoted experimental hepatocarcinogenesis. J Cell Biochem 88: 578–588, 2003

    Article  CAS  PubMed  Google Scholar 

  6. Sun Y: Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 8: 583–599, 1990

    Article  Google Scholar 

  7. Dhawan A, Mathur N, Seth PK: The effect of smoking and eating habit on DNA damage in Indian populations as measured in the comet assay. Mutat Res 474: 121–128, 2001

    Google Scholar 

  8. Kensler TW: Chemoprevention by inducers of carcinogen detoxification enzymes. Environ Health Perspect 105: 965–970, 1997

    Google Scholar 

  9. Ye L, Zhang Y: Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of phase II detoxification enzymes. Carcinogenesis 22: 1987–1992, 2001

    Google Scholar 

  10. Block G, Patterson B, Subar A: Fruit and vegetables, and cancer prevention: A review of epidemiological evidence. Nutr Cancer 18: 1–29, 1992

    CAS  PubMed  Google Scholar 

  11. Mittal R, Gupta RL: Invitro antioxidants activity of piperine. Methods Find Exp Clin Pharmacol 22: 163–167, 2000

    Google Scholar 

  12. Reen RK, Roesch SF, Kiefer F, Wiehel F, Singh J: Piperine impairs cytochrome P4501A1 activity by direct intraction with the enzyme and not by down regulation of gene expression in the rat hepatoma 5L cell lines. Biochem Biophys Res Commun 218: 562–569, 1996

    Google Scholar 

  13. Allameh A, Saxena M, Biswas G, Raj HG, Singh J, Srivastava N: Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. Cancer Lett 61: 195–199, 1992

    Google Scholar 

  14. Nakini N, Sabitha K, Viswanathan P, Menon VP, Spices and glycoproteins metabolism in experimental colon cancer in rats. Med Sci Res 26: 781–784, 1998

    Google Scholar 

  15. Chu E, Chang JP, Wang CY: Modulation effect of piperine on B(a)P cytotoxicity and DNA adduct formation in lung cells. Food Chem Toxicol 32: 373–377, 1994

    Google Scholar 

  16. Selvendiran K, Prince Vijeya Singh J, Babakrishnan K, Sakthisekaran D: Cytoprotective effect of piperine against B(a)p induced lung cancer with reference to antioxidant systems in Swiss albino mice. Fitoterapia 74: 109–115, 2003

    Google Scholar 

  17. Selvendiran K, Padmavathi R, Sakthisekaran D: Inhibition of genotoxicity by piperine in Swiss albino mice. Fitoterapia (in press)

  18. Selvendiran K, Senthilnathan P, Magesh V, Sakthisekaran D: Modulatory effect of piperine on altered mitochotrial antioxidant system in B(a)p induced lung carcinogenesis in Swiss albino mice. Phytomedicine 11: 85–89, 2004

    Google Scholar 

  19. Selvendiran K, Prince Vijeya Singh J, Mumtaz Banu S, Sakthisekaran D: Piperine induce apoptosis and alterd marker enzymes in B(a)p induced lung carcinogenesis. Cancer Detect Prev (in press)

  20. Pick E, Keisari EY: Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages induction by multiple nonphagocytic stimuli. Cell Immunol 59: 301–318, 1981

    Google Scholar 

  21. Zhitkovich A, Costa M: Simple, sensitive assays to detect DNA-protein cross links in intact cells and in vivo. Carcinogenesis 13: 1485–1489, 1992

    Google Scholar 

  22. Singh NB, Mc coy MT, Tice RR, Schneider EL: A simple technique for low levels of DNA-damage in individual cells. Exp Cell Res 175: 184–191, 1988

    CAS  PubMed  Google Scholar 

  23. Benson A, Hunkeler M, Talalay P: Increase of NADPH quinone reductase by dietary nutrient: Possible role in protection against carcinogenesis and toxicity. Proc Nalt Acad Sci USA 5216–5220, 1980

  24. Liquita MG, Sanchez Pozzim EJ, Cotania VA, Mottino AD: Analysis of p-nitrophenol glucoridinationb in hepatic cytosolic fraction in rats. Biochem Pharmacol 47: 1179–1185, 1994

    Google Scholar 

  25. Habig WH, Pabst MJ, Jokoby WB: Glutathione S-transferase. The first enzymatic step in mercapteric acid formation. J Biol Chem 249: 7130–7139, 1974

    Google Scholar 

  26. Sikkim H, Mulee B: Lipid peroxidation and antioxidant enzymes in the blood of rats treated with Benzo(a)pyrene. Chem Biol Interact 127: 139–150, 2000

    Google Scholar 

  27. Thirunavukkarasu C, Princevijeyasingh J, Selvendiran K, Sakthisekaran D: Chemopreventive efficacy of selenium against DEN-induced hepatoma in albino rats. Cell Biochem Funct 19: 265–271, 2001

    Article  CAS  PubMed  Google Scholar 

  28. Reddy AC, Lokesh AR: Studies on spices principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell Biochem 111: 117–124, 1992

    Google Scholar 

  29. Kyu BK, Byung ML: Oxidative stress to DNA, protein and antioxidant enzymes in rats treated with Benzo(a)pyrene. Cancer Lett 113: 205–212, 1997

    Google Scholar 

  30. Nancy LO, Maochiu S, Ramakrishnan N, Yan Xue L: The formation, identification and significance of DNA protein cross-links in mammalian cells. Cancer 53: 135–140, 1987

    Google Scholar 

  31. Costa M: Analysis of DNA-protein complexes induced by chemical carcinogens. J Cell Biochem 44: 127–135, 1990

    Google Scholar 

  32. Andreas H, Guntes S: Comparative investigation of the genetic effects of metals in the single cell gel electrophoreses assay. Environ Mol Mutagen 23: 299–305, 1994

    Google Scholar 

  33. Mikhail F, Denissenko K, Annie P, Moon-shong T, Gerd PP: Preferential formation of Benzo(a)pyrene-DNA adducts at lung cancer mutational hotspots in P53. Science 274: 430–432, 1996

    Google Scholar 

  34. Watten berg W, Wideman S, Richard D, Estensen C, Vernon E, Gary GK: Chemoprevention of pulmonary carcinogenesis by budenoside in mice. Cancer Res 57: 5489–5492, 1997

    Google Scholar 

  35. Heather EK, Suryanarayana V, Vulimiri LM, William H, Johnson JR, Christian P, Whitman, Dicriovanni S: Oral, administration of naturally occuring coumarins leads to altered phase I and II enzyme activities and reduced DNA adduct formation of polycyclic aromatic hydrocarbons in various tissues of SENCAR mice. Carcinogenesis 22: 3–82, 2001

    Google Scholar 

  36. Reen RK, Singh J: Invitro and invivo inhibition of pulmonary cytochrome P450 activities by piperine. I. J Exp Biol 29: 568–573, 1991

    Google Scholar 

  37. Annu K, Neelima T, Usha Z, Bedi KL: Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa. Mol Cell Biochem 189: 113–118, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India

    Karuppaiyah Selvendiran, Syed Mumtaz Banu & Dhanapal Sakthisekaran

Authors
  1. Karuppaiyah Selvendiran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed Mumtaz Banu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dhanapal Sakthisekaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Selvendiran, K., Banu, S.M. & Sakthisekaran, D. Oral supplementation of piperine leads to altered phase II enzymes and reduced DNA damage and DNA-protein cross links in Benzo(a)pyrene induced experimental lung carcinogenesis. Mol Cell Biochem 268, 141–147 (2005). https://doi.org/10.1007/s11010-005-3702-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-3702-z

Key words

Search

Navigation