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01-11-2012 | Original Research Paper

Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model

Authors: P. Anandakumar, S. Kamaraj, S. Jagan, G. Ramakrishnan, S. Asokkumar, C. Naveenkumar, S. Raghunandhakumar, T. Devaki

Published in: Inflammation Research | Issue 11/2012

Abstract

Objective

Lung cancer is a serious health problem in most developed countries and its incidence rate is profusely increasing. Capsaicin, a component of red chilli and red pepper has been studied widely for its chemopreventive properties. The aim of the present study is to explore the anti-tumor activity of capsaicin against benzo(a)pyrene-induced lung tumorigenesis in Swiss albino mice.

Materials and methods

Benzo(a)pyrene was administered orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. Hematological study (hemoglobin content, RBC, WBC count and differential count), histochemical analysis of mast cells and Western blot analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) were carried out.

Results

Hematological parameters and the histochemical analysis of mast cells showed abnormal changes, and the immunoblotting analysis revealed increased protein expression of TNF-α, IL-6, COX-2 and NF-κB in lung cancer-challenged mice administered with benzo(a)pyrene. Capsaicin (10 mg/kg body weight) supplementation to lung cancer bearing mice considerably prevented all the above abnormalities.

Conclusion

The results of the present study indicate the protective effect of capsaicin against benzo(a)pyrene-induced lung carcinogenesis in mice.

Magesh V, Jayapal PV, 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;287:127–35.PubMedCrossRef

Stephen S, Pramod Upadhaya, Mingyao Wang, Robin Bliss L, Edward Mcintee J, Patrick Kenney MJ. Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine and myo-inositol, individually and in combination. Carcinogenesis. 2002;29:1455–61.

Hans peter W, Deuter M, Imilda E. Chemoprevention of tobacco smoke induced lung carcinogenesis in mice. Carcinogenesis 2000; 21:977–982.

Anto RJ, Mukhopadyah A, Denning K, Aggarwal BB. Curcumin induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis. 2002;23:143–50.PubMedCrossRef

Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 1991;43(2):143–201.PubMed

Holzer P. The pharmacological challenge to the transient receptor potential vanilloid-1 (TRPV1) nocisensor. Br J Pharmacol. 2008;155(8):1145–62.PubMedCrossRef

Pinter E, Helyes Z, Szolcsányi J. Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther. 2006;112(2):440–56.PubMedCrossRef

Modly CE, Das M, Don PS, Marcelo CS, Mukhtar H, Bickers DR. Capsaicin as an in vitro inhibitor of benzo(a)pyrene metabolism and its DNA binding in human and murine keratinocytes. Drug Metab Dispos. 1986;14:413–6.PubMed

Zhang Z, Hamilton SM, Stewart C, Strother A, Teel RW. Inhibition of liver microsomal cytochrome P-450 activity and metabolism of the tobacco-specific nitrosamine NNK by capsaicin and ellagic acid. Anticancer Res. 1993;13:2341–6.PubMed

10.

Teel RW, Zhang Z, Uynh H, Hamilton SM. Effects of capsaicin on the metabolic activation of heterocyclic amines and on cytochrome P450 1A2 activity in hamster liver microsomes. Proc Am Assoc Cancer Res. 1997;38:363.

11.

De AK, Ghosh JJ. Capsaicin pretreatment protects free radical induced rat lung damage on exposure to gaseous chemical lung irritants. Phytother Res. 1993;7:87–9.CrossRef

12.

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

13.

Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Devaki T. Effect of capsaicin on glucose metabolism studied in experimental lung carcinogenesis. Nat Prod Res. 2009;23(8):763–74.PubMedCrossRef

14.

Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Devaki T. Chemopreventive task of capsaicin against benzo(a)pyrene induced lung cancer in Swiss albino mice. Basic Clin Pharmacol Toxicol. 2009;104(5):360–5.PubMedCrossRef

15.

Dacie JV, Lewis SM. Practical haematology. 7th ed. ELBS with Churchill Living stone: England; 1991. pp 37–85.

16.

D’Armour FE, Blood FR, Belden DA. The manual for laboratory works in mammalian physiology. 3rd ed. The University of Chicago Press: Illinois, Chicago; 1965.

17.

Wintrobe MM, Lee GR, Boggs DR, Bithel TC, Athens JW, Foerster J. Clinical Hematology. 5th ed. Les & Febiger: Philadelphia; 1961.

18.

Ranieri G, Labriola A, Achille G, Florio G, Zito AF, Grammatica L, et al. Microvessel density, mast cell density and thymidine phosphorylase expression in oral squamous carcinoma. Int J Oncol. 2002;21(6):1317–23.PubMed

19.

Ramakrishnan G, Elinos-Baez CM, Jagan S, Augustine TA, Kamaraj S, Anandakumar P, Devaki T. Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma. Mol Cell Biochem. 2008;313:53–61.PubMedCrossRef

20.

Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst. 1999;91:1616–34.PubMedCrossRef

21.

Brown JM. The hypoxic cell: a target for selective cancer therapy—Eighteenth Bruce F Cain memorial award lecture. Cancer Res. 1999;59:5863–70.PubMed

22.

Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Caner Inst. 2001;93:266–76.CrossRef

23.

Gangar SC, Sandhir R, Koul A. Effects of Azadirachta indica on certain hematological parameters during benzo(a)pyrene induced murine forestomach tumorigenesis. Eur Rev Med Pharmacol. 2010;14:1055–72.

24.

Ariztia EV, Lee CJ, Gogoi R, Fishman DA. The tumor microenvironment: key to early detection. Crit Rev Clin Lab Sci. 2006;43:393–425.PubMedCrossRef

25.

Philip M, Rowley DA, Schreiber H. Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol. 2004;14:433–9.PubMedCrossRef

26.

Noguchi M, Hiwatashi N, Liu Z, Toyota T. Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease. Gut. 1998;43:203–9.PubMedCrossRef

27.

Ben-Baruch A. Host microenvironment in breast cancer development: inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor-microenvironment interactions. Breast Cancer Res. 2003;5:31–6.PubMedCrossRef

28.

Tselepis C, Perry I, Dawson C, Hardy R, Darnton SJ, McConkey C, Stuart RC, Wright N, Harrison R, Jankowski JA. Tumour necrosis factor-a in Barrett’s oesophagus: a potential novel mechanism of action. Oncogene. 2002;21:6071–81.PubMedCrossRef

29.

Rose-John S, Schooltink H. Cytokines are a therapeutic target for the prevention of inflammation-induced cancers. Recent Results Cancer Res. 2007;174:57–66.PubMedCrossRef

30.

Kai H, Kitadai Y, Kodama M, Cho S, Kuroda T, Ito M, Tanaka S, Ohmoto Y, Chayama K. Involvement of proinflammatory cytokines IL-1b and IL-6 in progression of human gastric carcinoma. Anticancer Res. 2005;25:709–13.PubMed

31.

Schneider MR, Hoeflich A, Fischer JR, Wolf E, Sordat B, Lahm H. Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett. 2000;151:31–8.PubMedCrossRef

32.

Chung YC, Chang YF. Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol. 2003;83:222–6.PubMedCrossRef

33.

Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol. 2006;72:1605–21.PubMedCrossRef

34.

Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, et al. Increased expression of cyclooxygenase-2 occurs frequently in human lung cancer, specifically in adenocarcinomas. Cancer Res. 1998;58:3761–4.PubMed

35.

Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res. 1997;57:1276–80.PubMed

36.

Yip-Schneider MT, Barnard DS, Billings SD, Cheng L, Heilman DK, Lin A, Marshall SJ, Crowell PL, Marshall MS, Sweeney CJ. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis. 2000;21:139–46.PubMedCrossRef

37.

Naylor MS, Stamp GW, Foulkes WD, Eccles D, Balkwill FR. Tumor necrosis factor and its receptors in human ovarian cancer. Potential role in disease progression. J Clin Invest. 1993;91:2194–206.PubMedCrossRef

38.

Lawrence T. Inflammation and cancer: a failure of resolution? Trends Pharmacol Sci. 2007;28:162–5.PubMedCrossRef

39.

Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y. NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431:461–6.PubMedCrossRef

40.

Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res. 2006;4:221–33.PubMedCrossRef

41.

Melendez AJ, Harnett MM, Pushparaj PN, et al. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 2007;13:1211–8.CrossRef

42.

Theoharides TC, Conti P. Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 2004;25:235–41.PubMedCrossRef

43.

Tan S-Y, Fan Y, Luo H-S, Shen Z-X, Guo Y, Zhao L-J. Prognostic significance of cell infiltrations of immunosurveillance in colorectal cancer. World J Gastroenterol. 2005;11:1210–4.PubMed

44.

Takanami I, Takeuchi K, Naruke M. Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma. Cancer. 2000;15:2686–92.CrossRef

Title: Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model
Authors: P. Anandakumar
S. Kamaraj
S. Jagan
G. Ramakrishnan
S. Asokkumar
C. Naveenkumar
S. Raghunandhakumar
T. Devaki
Publication date: 01-11-2012
Publisher: SP Birkhäuser Verlag Basel
Published in: Inflammation Research / Issue 11/2012
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-012-0511-1

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Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model

Abstract

Objective

Materials and methods

Results

Conclusion

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Abstract

Objective

Materials and methods

Results

Conclusion

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