SpringerLink
Log in

Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice

  • Original research article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Chemoprevention is considered as one of the most promising and realistic approaches in the prevention of lung cancer. Chrysin, a naturally occurring dietary flavone widely found in Passiflora family of plants and honey, has been studied extensively for its chemopreventive properties. The objective of present study is to divulge the chemopreventive role of chrysin against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in Swiss albino mice.

Methods

B(a)P was administered orally (50 mg/kg body weight) twice a week for four weeks to induce lung cancer in mice. The body weight, lung weight, tumor incidence, lipid peroxidation, carcinoembryonic antigen, enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and non-enzymatic antioxidants (reduced glutathione, vitamin E and vitamin C) were estimated. Further, histopathological analysis of lung tissue and western blotting analysis of PCNA, COX-2 and NF-κB were also carried out.

Results

Administration of B(a)P resulted in increased lipid peroxides and carcinoembryonic antigen with concomitant decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants. Chrysin treatment (250 mg/kg body weight) significantly attenuated all these changes thereby showing potent anti lung cancer effect. Further, the anticancer effect of chrysin was confirmed by histopathology of lungs, and immunoblotting analysis of PCNA, COX-2 and NF-κB, where chrysin supplementation downregulated the expression of these proteins and maintained cellular homeostasis.

Conclusion

Overall, these findings confirm the chemopreventive potential of chrysin against B(a)P induced lung cancer in Swiss albino mice.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.

    PubMed  Google Scholar 

  2. Ferlay J, Ervik M, Dikshit R, Eser S, Mathers C. Cancer incidence and mortality worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2012, GLOBOCAN 2012 v1.0 [accessed 18.05.15].

  3. Hoffmann D, Hoffmann I, El-Bayoumy K. The less harmful cigarette: a controversial issue. A tribute to Ernst L. Wynder. Chem Res Toxicol 2001;14(7): 767–90.

    Article  CAS  PubMed  Google Scholar 

  4. Kasala ER, Bodduluru LN, Barua CC, Shekhar SC, Gogoi R. Benzo (a) pyrene induced lung cancer: role of dietary phytochemicals in chemoprevention. Pharmacol Rep 2015. http://dx.doi.org/10.1016/j.pharep.2015.03.004.

  5. Gelboin HV. Benzo [alpha] pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiol Rev 1980;60(4):1107–66.

    Article  CAS  PubMed  Google Scholar 

  6. Penning TM, Burczynski ME, Hung CF, McCoull KD, Palackal NT, Tsuruda LS. Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation: generation of reactive and redox active o-quinones. Chem Res Toxicol 1999;12(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  7. Bodduluru LN, Kasala ER, Thota N, Barua CC, Sistla R. Chemopreventive and therapeutic effects of nimbolide in cancer: the underlying mechanisms. Toxicol In Vitro 2014;28(5):1026–35.

    Article  CAS  PubMed  Google Scholar 

  8. Block G, Patterson B, Subar A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 1992;18(1):1–29.

    Article  CAS  PubMed  Google Scholar 

  9. Keith RL. Chemoprevention of lung cancer. Proc Am Thorac Soc 2009;6(2): 187–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hu R, Kong ANT. Activation of MAP kinases, apoptosis and nutrigenomics of gene expression elicited by dietary cancer-prevention compounds. Nutrition 2004;20(1):83–8.

    Article  CAS  PubMed  Google Scholar 

  11. Kamaraj S, Ramakrishnan G, Anandakumar P, Jagan S, Devaki T. Antioxidant and anticancer efficacy of hesperidin in benzo (a) pyrene induced lung carcinogenesis in mice. Invest New Drugs 2009;27(3):214–22.

    Article  CAS  PubMed  Google Scholar 

  12. Devadoss D, Ramar M, Chinnasamy A. Galangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status. Arch Pharm Res 2014; 1–11.

  13. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev 2003;23(4):519–34.

    Article  CAS  PubMed  Google Scholar 

  14. Lapidot T, Walker MD, Kanner J. Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro. J Agric Food Chem 2002;50(25):7220–5.

    Article  CAS  PubMed  Google Scholar 

  15. Kim EJ, Kwon KJ, Park JY, Lee SH, Moon CH, Baik EJ. Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2. Brain Res 2002;941(1–2): 1–10.

    Article  CAS  PubMed  Google Scholar 

  16. Rauter AP, Martins A, Borges C, Mota-Filipe H, Pinto R, Sepodes B, et al. Antihyperglycaemic and protective effects of flavonoids on streptozotocin-induced diabetic rats. Phytother Res 2010;24:S133–8.

    Article  PubMed  Google Scholar 

  17. Khoo BY, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci 2010;11(5):2188–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kasala ER, Bodduluru LN, Madana RM, Athira KV, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives. Toxicol Lett 2015;233(2):214–25.

    Article  CAS  PubMed  Google Scholar 

  19. Wattenberg LW, Leong JL. Inhibition of the carcinogenic action of benzo (a) pyrene by flavones. Cancer Res 1970;30(7):1922–5.

    CAS  PubMed  Google Scholar 

  20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.

    Article  CAS  PubMed  Google Scholar 

  21. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351–8.

    Article  CAS  PubMed  Google Scholar 

  22. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973;179(4073):588–90.

    Article  CAS  PubMed  Google Scholar 

  23. Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol 1985;113: 484–90.

    Article  CAS  PubMed  Google Scholar 

  24. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70–7.

    Article  CAS  PubMed  Google Scholar 

  25. Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol 1984;105:138–47.

    Article  CAS  PubMed  Google Scholar 

  26. Omaye ST, Turnbull JD, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 1979;62:3–11.

    CAS  PubMed  Google Scholar 

  27. Boorman GA. Pathology of the Fischer rat: reference and atlas. Academic Press; 1990.

  28. Dosil-Diaz O, Ruano-Ravina A, Gestal-Otero JJ, Barros-Dios JM. Consumption of fruit and vegetables and risk of lung cancer: a case-control study in Galicia, Spain. Nutrition 2008;24(5):407–13.

    Article  PubMed  Google Scholar 

  29. Kasala ER, Bodduluru LN, Barua CC. Nimbolide inhibits invasion of breast cancer. Cell Prolif 2015;48(2):117–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kasala ER, Bodduluru LN, Barua CC, Gogoi R. Chrysin and its emerging role in cancer drug resistance. Chem Biol Interact 2015;236:7–8.

    Article  CAS  PubMed  Google Scholar 

  31. Ravichandran N, Suresh G, Ramesh B, Siva GV. Fisetin, a novel flavonol attenuates benzo (a) pyrene-induced lung carcinogenesis in Swiss albino mice. Food Chem Toxicol 2011;49(5):1141–7.

    Article  CAS  PubMed  Google Scholar 

  32. Tessitore L, Costelli P, Baccino FM. Pharmacological interference with tissue hypercatabolism in tumour-bearing rats. Biochem J 1994;299(Pt 1):71–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Magesh V, Singh JP, Selvendiran K, Ekambaram G, Sakthisekaran D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol Cell Biochem 2006;287(1–2):127–35.

    Article  CAS  PubMed  Google Scholar 

  34. Kim HS, Kwack SJ, Lee BM. Lipid peroxidation, antioxidant enzymes, and benzo [a] pyrene-quinones in the blood of rats treated with benzo [a] pyrene. Chem Biol Interact 2000;127(2):139–50.

    Article  CAS  PubMed  Google Scholar 

  35. Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, et al. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 2000;148(2–3):187–97.

    Article  CAS  PubMed  Google Scholar 

  36. Kamaraj S, Vinodhkumar R, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T. The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo (a) pyrene. Biol Pharm Bull 2007;30(12): 2268–73.

    Article  CAS  PubMed  Google Scholar 

  37. Marklund SL, Westman NG, Lundgren E, Roos G. Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res 1982;42(5):1955–61.

    CAS  PubMed  Google Scholar 

  38. Deponte M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 2013;1830(5):3217–66.

    Article  CAS  PubMed  Google Scholar 

  39. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Naveenkumar C, Asokkumar S, et al. Capsaicin alleviates the imbalance in xenobiotic metabolizing enzymes and tumor markers during experimental lung tumorigenesis. Mol Cell Biochem 2009;331(1–2):135–43.

    Article  CAS  PubMed  Google Scholar 

  40. Adly AAM. Oxidative stress and disease: an updated review. Res J Immunol 2010;3:129–45.

    Article  CAS  Google Scholar 

  41. Karaoz E, Gultekin F, Akdogan M, Oncu M, Gokcimen A. Protective role of melatonin and a combination of vitamin C and vitamin E on lung toxicity induced by chlorpyrifos-ethyl in rats. Exp Toxicol Pathol 2002;54(2):97–108.

    Article  CAS  PubMed  Google Scholar 

  42. Sakao Y, Tomimitsu S, Takeda Y, Natsuaki M, Itoh T. Carcinoembryonic antigen as a predictive factor for postoperative tumor relapse in early-stage lung adenocarcinoma. Eur Cardiothorac Surg 2004;25(4):520–2.

    Article  Google Scholar 

  43. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 1987;326(6112):515–7.

    Article  CAS  PubMed  Google Scholar 

  44. Dworakowska D, Gozdz S, Jassem E, Badzio A, Kobierska G, Urbaniak A, et al. Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer. Lung Cancer 2002;35(1):35–41.

    Article  CAS  PubMed  Google Scholar 

  45. Miyamoto S, Yasui Y, Ohigashi H, Tanaka T, Murakami A. Dietary flavonoids suppress azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db mice. Chem Biol Interact 2010;183(2):276–83.

    Article  CAS  PubMed  Google Scholar 

  46. Pantano C, Reynaert NL, van der Vliet A, Janssen-Heininger YM. Redox-sensitive kinases of the nuclear factor-kappaB signaling pathway. Antioxid Redox Signal 2006;8(9–10):1791–806.

    Article  CAS  PubMed  Google Scholar 

  47. Woo KJ, Jeong YJ, Inoue H, Park JW, Kwon TK. Chrysin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression through the inhibition of nuclear factor for IL-6 (NF-IL6) DNA-binding activity. FEBS Lett 2005;579(3): 705–11.

    Article  CAS  PubMed  Google Scholar 

  48. Khan MS, Devaraj H, Devaraj N. Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats. Toxicol Appl Pharmacol 2011;251(1):85–94.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India

    Eshvendar Reddy Kasala, Lakshmi Narendra Bodduluru, Rajaram Mohanrao Madhana, Vicky Dahiya, Mukesh Kumar Budhani, Ramana Reddy Mallugari & Suseela Reddy Maramreddy

  2. Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, India

    Chandan C. Barua

  3. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India

    Ranadeep Gogoi

Authors
  1. Eshvendar Reddy Kasala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lakshmi Narendra Bodduluru
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chandan C. Barua
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajaram Mohanrao Madhana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vicky Dahiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mukesh Kumar Budhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ramana Reddy Mallugari
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Suseela Reddy Maramreddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ranadeep Gogoi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eshvendar Reddy Kasala.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kasala, E.R., Bodduluru, L.N., Barua, C.C. et al. Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. Pharmacol. Rep 68, 310–318 (2016). https://doi.org/10.1016/j.pharep.2015.08.014

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2015.08.014

Keywords

Search

Navigation