Abstract
Nowadays, in developing countries like India, incidence of lung cancer is increasing rapidly, and as a consequence it has become the most common cause of malignancy-associated death. This study is aimed to evaluate the therapeutic efficacy of beta-ionone (ION), a precursor for carotenoids against benzo(a)pyrene [B(a)P]-induced lung carcinogenesis. B(a)P (50 mg/kg body weight, orally twice a week for 4 successive weeks)-induced lung cancer in mice was assessed both in tissue and serum in terms of increase LPO and tissue marker enzymes, such as aryl hydrocarbon hydroxylase, γ-glutamyl transpeptidase, 5′-nucleotidase, and lactate dehydrogenase, and serum tumor markers such as carcinoembryonic antigen and neuron-specific enolase with concordant decrease in activities of tissue enzymic and non-enzymic antioxidants were observed on the treatment of ION (60 mg/kg body weight, orally twice a week for 16 weeks) significantly attenuated LPO and restored all cancer marker enzymes and antioxidants levels to near normal, which indicates the anticancer effect of ION. This was further confirmed by histological staining of argyrophilic nucleolar organizer region and histopathological analysis of lung tissue, immunohistochemical and immunoblot analysis of proliferating cell nuclear antigen. Overall findings suggested that the ION effectively ameliorated the lung carcinogenesis, which is attributed to the antiproliferative and antioxidant potential through free radical scavenging property.
Similar content being viewed by others
References
Tang N, Wu Y, Ma J, Wang B, Yu R (2010) Coffee consumption and risk of lung cancer: a meta-analysis. Lung Cancer 67:17–22
National Cancer Institute SEER data. Available at: http://seer.cancer.gov/statistics/. Accessed 20 June 2009
Delgado-Saborit JM, Stark C, Harrison RM (2010) Carcinogenic potential, levels and sources of polycyclic aromatic hydrocarbon mixtures in indoor and outdoor environments and their implications for air quality standards. Environ Int 37:383–392
Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Naveenkumar C, Asokkumar S et al. (2009) Capsaicin alleviates the imbalance in xenobiotic metabolizing enzymes and tumor markers during experimental lung tumorigenesis. Mol Cell Biochem. doi:10.1007/s11010-009-0151-0
Tsuji G, Takahara M, Uchi H, Takeuchi S, Mitoma C, Moroi Y, Furue M et al (2011) An environmental contaminant, benzo(a)pyrene, induces oxidative stress-mediated interleukin-8 production in human keratinocytes via the aryl hydrocarbon receptor signaling pathway. J Dermatol Sci 62(1):42–49
Kamaraj S, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T (2010) Modulatory effect of hesperidin on benzo(a)pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9. Eur J Pharmacol. doi:10.1016/j.ejphar.2010.09.017
Hail N Jr, Cortes M, Drake EN, Spallholz JE (2008) Cancer chemoprevention: a radical perspective. Free Radic Biol Med 45:97–110
Milner JA (2008) Nutrition and cancer: essential elements for a roadmap. Cancer Lett 269:189–198. doi:10.1016/j.canlet05.030
Cardozo MT, de Conti A, Ong TP, Scolastici C, Purgatto E, Horst MA et al. (2010) Chemopreventive effects of β-ionone and geraniol during rat hepatocarcinogenesis promotion: distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA. J Nutr Biochem. doi:10.1016/j.jnutbio.2009.12.007
Kim MO, Moon DO, Kang CH, Kwon TK, Choi YH, Kim GY (2010) β-Ionone enhances TRAIL-induced apoptosis in hepatocellular carcinoma cells through Sp1-dependent upregulation of DR5 and downregulation of NF-κB Activity. Mol Cancer Ther 9:833. doi:10.1158/1535-7163.MCT-09-061
Kamaraj S, Ramakrishnan G, Anandakumar P, Jagan S, Devaki T (2008) Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice. Invest New Drugs. doi:10.1007/s10637-008-9159-7
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. doi:10.1016/0003-2697(79)90738-3
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474. doi:10.1111/j.1432-1033.1974.tb03714.x
Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394. doi:10.1016/0003-2697(72)90132-7
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590
Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78
Horn HD, Burn FH (1978) In: Bergmeyer HV (ed) Methods in enzymology. Academic Press, New York, p 877
Desai ID (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol 105:138–147
Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62:3–11
Ramakrishnan G, Elinos-Baez CM, Jagan S, Augustine TA, Kamaraj S, Anandakumar P et al (2008) Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma. Mol Cell Biochem 313:53–61. doi:10.1007/s11010-008-9741-5
Ploton D, Menager M, Jeannesson P, Himber G, Pigeon F, Adnet JJ (1986) Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer regions at the optical level. Histochem J 18:5–14. doi:10.1007/BF01676192
Singh SV, Benson PJ, Hu X, Pal A, Xia H, Srivastava SK et al (1998) Gender-related differences in susceptibility of A/J mouse to benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis. Cancer Lett 128:197–204
Kim HS, Kwack SJ, Lee BM (2000) Lipid peroxidation, antioxidant enzymes, and benzo[a]pyrene-quinones in the blood of rats treated with benzo[a]pyrene. Chem Biol Interact 127:139–150. doi:10.1016/S0009-2797(00)00177-0
Liu JR, Dong HW, Sun XR, Wang Q, Sun WG, Parry JW et al (2010) Effects of β-ionone on mammary carcinogenesis and antioxidant status in rats treated with DMBA. Nutr Cancer 62:58–65. doi:10.1080/01635580903191510
Sirri V, Roussel P, Trerè D, Derenzini M, Hernandez-Verdun D (1995) Amount variability of total and individual Ag-NOR proteins in cells stimulated to proliferate. J Histochem Cytochem 43:887–893
Feng Q, Kumagai T, Torii Y, Nakamura Y, Osawa T, Uchida K (2001) Anticarcinogenic antioxidants as inhibitors against intracellular oxidative stress. Free Radic Res 35:779–788
Gosset P, Garçon G, Casset A, Fleurisse L, Hannothiaux MH, Creusy C et al (2003) Benzo(a)pyrene-coated onto Fe2O3 particles-induced apoptotic events in the lungs of Sprague-Dawley rats. Toxicol Lett 143:223–232. doi:10.1016/S0378-4274(03)00153-X
de Zwart LL, Meerman JH, Commandeur JN, Vermeulen NP (1999) Biomarkers of free radical damage applications in experimental animals and in humans. Free Radic Biol Med 26:202–226. doi:10.1016/S0891-5849(98)00196-8
Sorokina LV, Solyanik GI, Pyatchanina TV (2010) The evaluation of prooxidant and antioxidant state of two variants of lewis lung carcinoma: a comparative study. Exp Oncol 32(4):249–253
Gupta KB, Tandon S, Garg V, Lai H (2000) Plasma glutathione-S-transferase activity in lung malignancy. Ind J Tuberc 47:227
Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Vinodhkumar R, Devaki T (2008) Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer. Biomed Pharmacother 62:390–394
Hanigan MH, Ricketts WA (1993) Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. Biochemistry 32:6302–6306
Foa P, Fornier M, Miceli R, Seregni E, Santambrogio L, Nosotti M et al (1994) Tumor markers CEA, NSE, SCC, TPA and CYFRA 21.1 in resectable non-small cell lung cancer. Anticancer Res 19:3613–3618
Ronkainen H, Soini Y, Vaarala MH, Kauppila S, Hirvikoski P (2010) Evaluation of neuroendocrine markers in renal cell carcinoma. Diagn Pathol 5:28
Keshgegian AA, Cnaan A (1995) Proliferation markers in breast carcinoma. Mitotic figure count, S-phase fraction, proliferating cell nuclear antigen, Ki-67 and MIB-1. Am J Clin Pathol 104:42–49
Jagan S, Ramakrishnan G, Anandakumar P, Kamaraj S, Devaki T (2008) Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma. Mol Cell Biochem. doi:10.1007/s11010-008-9876-4
Orellana-Bustos AI, Espinoza-Santander IL, Franco-Martínez ME, Lobos-James-Freyre N, Ortega-Pinto AV (2004) Evaluation of keratinization and AgNORs counts in exfoliative cytology of normal mucosa from smokers and non-smokers. Med Oral 9:197–203
Uno T, Hashimoto S, Shimono M (1998) A study of the proliferative activity of the long junctional epithelium using argyrophilic nucleolar organizer region (AgNORs) staining. J Periodont Res 33:298–309
Janakiram NB, Cooma I, Mohammed A, Steele VE, Rao CV (2008) Beta-ionone inhibits colonic aberrant crypt foci formation in rats, suppresses cell growth, and induces retinoid X receptor-alpha in human colon cancer cells. Mol Cancer Ther 7:181–190
Acknowledgment
The first author S. Asokkumar gratefully acknowledges University Grants Commission (UGC), for Junior Research Fellowship, New Delhi, India and University Research Fellowship from University of Madras, for financial assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Asokkumar, S., Naveenkumar, C., Raghunandhakumar, S. et al. Antiproliferative and antioxidant potential of beta-ionone against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice. Mol Cell Biochem 363, 335–345 (2012). https://doi.org/10.1007/s11010-011-1186-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-011-1186-6