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Chemopreventive activity of lantadenes on two-stage carcinogenesis model in Swiss albino mice: AP-1 (c-jun), NFκB (p65) and P53 expression by ELISA and immunohistochemical localization

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Abstract

Lantadenes are pentacyclic triterpenoids isolated from leaves of Lantana camara L. and have antitumor activity. Lantadene A (LA) and methyl ester of LA (LAM) were earlier studied in the author’s lab for their chemopreventive effect on 7,12-dimethylbenz(a)anthracene (DMBA) followed by 12–O-tetradecanoylphorbol-13-acetate (TPA) induced squamous cell carcinoma incidence in Swiss albino mice. The present study was specially designed to initiate the involvement of the molecular targets in chemopreventive activity of these compounds. Skin lesions were induced by twice-weekly topical application of DMBA (100 nmol/100 μl of acetone) for 2 weeks followed by TPA (1.7 nmol/100 μl of acetone) on depilated back of mice for 20 weeks. LA and LAM were administered orally at a dose of 50 mg/kg body weight twice weekly, 1 week before DMBA application and continued for 20 weeks thereafter. A significant decrease in the incidence of number of lesions in mice was obtained in LA/LAM treated groups as compared to DMBA/TPA alone. Significant increase in the protein levels of c-jun, p65, and p53 by ELISA were observed in DMBA/TPA treated mice tumors whereas less expression was observed in LA and LAM treated tumors. Further immunohistochemical localization of transcription factors was studied which also showed less localization of c-jun, p65, and p53 in LA and LAM treated tumors as compared to localization in DMBA/TPA treated tumors. It can be inferred that LA and LAM chemopreventive activity may be linked to the deregulation of above molecular targets which warrants further studies in that direction.

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References

  1. Parker JN, Zhao W, Askins KJ, Broker TR, Chow LT (1997) Mutational analyses of differentiation-dependent human papillomavirus type 18 enhancer elements in epithelial raft cultures of neonatal foreskin keratinocytes. Cell Growth Differ 8:751–762

    PubMed  CAS  Google Scholar 

  2. Holeb AI, Fink DJ, Murphy GP (1991) American cancer society textbook of clinical oncology. Atlana American Cancer Society Inc., pp 456–465

  3. Shimada T (2006) Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet 21:257–276

    Article  PubMed  CAS  Google Scholar 

  4. Siebenlist U, Franzoso G, Brown K (1994) Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol 10:405–455

    Article  PubMed  CAS  Google Scholar 

  5. Angel P, Szabowski A, Schorpp-Kistner M (2001) Function and regulation of AP-1 subunits in skin physiology and pathology. Oncogene 20:2413–2423

    Article  PubMed  CAS  Google Scholar 

  6. Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4:131–136

    Article  CAS  Google Scholar 

  7. Jochum W, Passegué E, Wagner EF (2001) AP-1 in mouse development and tumorigenesis. Oncogene 20:2401–2412

    Article  PubMed  CAS  Google Scholar 

  8. Ozanne BW, McGarry L, Spence HJ, Johnston I et al (2000) Transcriptional regulation of cell invasion: AP-1 regulation of a multigenic invasion programme. Eur J Cancer 36:1640–1648

    Article  PubMed  CAS  Google Scholar 

  9. Suzuki T, Murakami M, Onai N, Fukuda F et al (1994) Analysis of AP-1 function in cellular transformation pathways. J Virol 68:3527–3535

    PubMed  CAS  Google Scholar 

  10. Lamb RF, Hennigan RF, Turnbull K, Katsanakis KD, MacKenzie ED, Birnie GD et al (1997) AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44. Mol Cell Biol 17:963–976

    PubMed  CAS  Google Scholar 

  11. Bone RC, Balk RA, Cerra FB et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies for sepsis. The ACCP/SCCM Conference Committee, American College of Chest Physicians/Society of Critical Care Medium. Chest 101:1644–1655

    Article  PubMed  CAS  Google Scholar 

  12. Ben-Shaul V, Lomintski L, Nyska A, Zurovsky Y, Berman M, Grossman S (2001) The effect of natural antioxidants, NAO and apocynin on oxidative stress in the rat heart following LPS challenge. Toxicol Lett 123:1–10

    Article  PubMed  CAS  Google Scholar 

  13. Barnes PJ (1997) Nuclear factor-κB. Int J Biochem Cell Biol 29:867–870

    Article  PubMed  CAS  Google Scholar 

  14. Levesque AA, Eastman A (2007) p53-based cancer therapies: is defective p53 the Achilles heel of the tumor? Carcinogenesis 28:13–20

    Article  PubMed  CAS  Google Scholar 

  15. Wattenberg LW (1997) An overview of chemoprevention: current status and future prospects. Proc Soc Exp Biol Med 216:133–141

    PubMed  CAS  Google Scholar 

  16. Singh DK, Lippman SM (1998) Cancer Chemoprevention, Part 1: retinoids and carotenoids and other classical antioxidants. Oncology (Willison Park) 12:1643–1660

    CAS  Google Scholar 

  17. Abdullaev GI (2001) Plant derived agent against cancer. In: Gupta SK (ed) Pharmacology and therapeutics in the new millennium, Narosa Publishing House, New Delhi, pp 345–354

  18. Kellof GJ, Boone CW, Crowell JA, Steel VE, Luvet R, Sigmen CC (1994) Chemopreventive drug development: perspectives and progress. Cancer Epidemiol Biomarkers Prev 3:85–98

    Google Scholar 

  19. Sharma OP, Vaid J, Sharma PD (1991) Natural products of the lantana plant- the present & prospects. J Sci Ind Res 48:471–478

    Google Scholar 

  20. Liu J (1995) Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 40:57–60

    Article  Google Scholar 

  21. Sharma M, Sharma PD (2006) Optimization of lantadene isolation & preparation of 22 β-hydroxy oleanolic acid. Chem Nat Comp 42:442–446

    Article  CAS  Google Scholar 

  22. Inada A, Nakanishi T, Tokuda H, Nishino H, Iwashina A, Sharma OP (1995) Inhibitory effects of Lantadenes & related triterpinoids on Epstein-Barr virus activation. Planta Med 61:558–560

    Article  PubMed  CAS  Google Scholar 

  23. Inada A, Nakanishi T, Tokuda T, Nishino H, Iwashina A, Sharma OP (1997) Anti-tumor promoting activities of Lantadenes on mouse skin tumors & mouse hepatic tumors. Planta Med 63:272–274

    Article  PubMed  CAS  Google Scholar 

  24. Sharma M, Sharma PD, Bansal MP (2007) Chemopreventive effect of Lantana camara leaf extract on 7,12-Dimethylbenz[a]anthracene-induced squamous cell carcinoma of skin in swiss albino mice. Pharma Biol 45:145–148

    Article  Google Scholar 

  25. Azuine MA, Bhide SV (1992) Chemopreventive effect of turmeric against stomach and tumors induced by chemical carcinogenesis in Swiss albino mice. Nutr Cancer 17:77–83

    PubMed  CAS  Google Scholar 

  26. Lowry OH, Rosenbrough NJ, Farr AL, Randell RJ (1955) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  27. Hess J, Angel P, Schorpp-Kistner M (2004) AP-1 subunits: quarrel and harmony among siblings. J Cell Sci 117:5965–5973

    Article  PubMed  CAS  Google Scholar 

  28. Aggarwal BB, Sethi G, Nair A, Ichikawa H (2006) Nuclear factor-κB: a holy grail in cancer prevention and therapy. Curr Sig Trans Therapy 1:25–52

    Article  CAS  Google Scholar 

  29. Asehnoune K, Strassheim D, Mitra S, Yeol-Kim M, Abraham E (2004) Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappaB. J Immunol 172:2522–2529

    PubMed  CAS  Google Scholar 

  30. Asakura M, Kitakaze M, Takashima S et al (2002) Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as new therapy. Nat Med 8:35–40

    Article  PubMed  CAS  Google Scholar 

  31. Bharti AC, Donato N, Singh S, Aggarwal BB (2003) Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and I kappa B alpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101:1053–1062

    Article  PubMed  CAS  Google Scholar 

  32. Agarwal ML, Taylor WR, Chernov MV, Chernova OB, Stark GR (1998) The p53 network. J Biol Chem 273:1–4

    Article  PubMed  CAS  Google Scholar 

  33. Mowat MR (1998) p53 in tumor progression: life, death and everything. Adv Cancer Res 74:25–48

    Article  PubMed  CAS  Google Scholar 

  34. Arora A, Siddiqui IA, Shuklka Y (2004) Modulation of p53 in 7,12-dimethylbenz[a]anthracene-induced skin tumors by diallyl sulfide in Swiss albino mice. Mol Cancer Ther 3:1459–1466

    PubMed  CAS  Google Scholar 

  35. Shin DM, Xu XC, Lippman SM et al (1997) Accumulation of p53 protein and retinoic acid receptor beta in retinoid chemoprevention. Clin Cancer Res 3:875–880

    PubMed  CAS  Google Scholar 

  36. Huang H, Ma WY, Goranson A, Dong Z (1999) Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis 20:237–242

    Article  PubMed  CAS  Google Scholar 

  37. She QB, Bode M, Ma WY, Chen NY, Dong Z (2001) Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res 61:1604–1610

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biophysics, Panjab University, Chandigarh, 160014, India

    Jagdeep Kaur & M. P. Bansal

  2. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India

    Manu Sharma & P. D. Sharma

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  1. Jagdeep Kaur
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  2. Manu Sharma
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  3. P. D. Sharma
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  4. M. P. Bansal
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Correspondence to M. P. Bansal.

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Kaur, J., Sharma, M., Sharma, P.D. et al. Chemopreventive activity of lantadenes on two-stage carcinogenesis model in Swiss albino mice: AP-1 (c-jun), NFκB (p65) and P53 expression by ELISA and immunohistochemical localization. Mol Cell Biochem 314, 1–8 (2008). https://doi.org/10.1007/s11010-008-9758-9

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