Skip to main content
SpringerLink
Log in

Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in mice

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

Abstract

Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12-dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA + croton oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA + croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p < 0.001). It could be concluded from our results that TA attenuates DMBA + croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Greenwald P, Milner JA, Anderson DE et al (2002) Micronutrient in cancer chemoprevention. Cancer Metastasis Rev 21:217–230

    Article  CAS  PubMed  Google Scholar 

  2. Soria JC, Kim ES, Fayette J et al (2003) Chemoprevention of lung cancer. Lancet Oncol 4:659–669

    Article  CAS  PubMed  Google Scholar 

  3. Cancer Research UK (2008). Skin cancer overview. http://info.Cancerresearchuk.org/healthyliving/sunsmart/skincancer/. Accessed 17 November 2008

  4. Wenk J, Brenneisen P, Meewes C, Wlaschek M, Peters T et al (2001) UV-induced oxidative stress and photoaging. Curr Probl Dermatol 29:83–94

    Article  CAS  PubMed  Google Scholar 

  5. Stefanie K, Ulrike B, Dennis N et al (2010) Quantification of ETS expose in hospitality workers who have never smoked. Environ Health 49:1096–1099

    Google Scholar 

  6. Saha D, Hait M (2012) An Ontological design: two stage mouse skin carcinogenesis induced by DMBA and promoted by croton oil. Asian J Res Pharm Sci 2:01–03

    Google Scholar 

  7. Di Giovanni J (1992) Multistage carcinogenesis in mouse skin. Pharm Ther 47:63–128

    Article  Google Scholar 

  8. Das RK, Bhattacharya S (2004) Inhibition of DMBA-croton oil two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate through modulation of cutaneous oxidative stress and inhibition of nitric oxide production. Asian Pac J Cancer 5:151–158

    Google Scholar 

  9. Berenblum I (1941) The mechanism of carcinogenesis: a study of the significance of the co-carcinogenic action and related phenomena. Cancer Res 1:807–814

    CAS  Google Scholar 

  10. Stoner GD, Mukhtar H (1995) Polphenols as cancer chemopreventive agents. J Cell Biochem 22:169–180

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Khan NS, Ahmad A, Hadi SM (2000) Antioxidant, prooxidant properties of tannic acid and its binding to DNA. Chem Biol Interact 125:177–189

    Article  CAS  PubMed  Google Scholar 

  13. Ferguson LR (2001) Role of plant polyphenols in genomic stability. Mutat Res 75:89

    Article  Google Scholar 

  14. Wu LC, Fan NC, Lin MH et al (2008) Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators. J Agric Food Chem 56:2341–2349

    Article  CAS  PubMed  Google Scholar 

  15. Andrade RG Jr, Dalvi LT, Silva JM Jr et al (2005) The antioxidant effect of tannic acid on the in vitro copper-mediated formation of free radicals. Arch Biochem Biophys 437:1–9

    Article  CAS  PubMed  Google Scholar 

  16. Chen SC, Chung KT (2000) Mutagenicity and antimutagenicity studies of tannic acid and its related compounds. Food Chem Toxicol 38:1–5

    Article  PubMed  Google Scholar 

  17. Huang WY, Cai YZ, Zhang Y (2010) Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer 62:1–20

    Article  PubMed  Google Scholar 

  18. Van der Logt EM, Roelofs HM, Nagengast FM et al (2003) Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens. Carcinogenesis 24:1651–1656

    Article  PubMed  Google Scholar 

  19. Ahmad ST, Sultana S (2012) Tannic acid mitigates cisplatin-induced nephrotoxicity in mice. Human Exp Toxicol 31:145–156

    Article  CAS  Google Scholar 

  20. Khan NS, Hadi SM (1998) Structural features of tannic acid important for DNA degradation in the presence of Cu(II). Mutagenesis 13:217

    Article  Google Scholar 

  21. Newmark H (1987) Plant phenolics as inhibitors of mutational and precarcinogenic events. Can J Physiol Pharmacol 65:461–466

    Article  CAS  PubMed  Google Scholar 

  22. Baer-Dubowska W, Gnojkowski J, Fenrych W (1997) Effect of tannic acid on benzo[a]pyrene-DNA adduct formation in mouse epidermis: comparison with synthetic gallic acid esters. Nutr Cancer 29:42–47

    Article  CAS  PubMed  Google Scholar 

  23. Baer-Dubowska W, Szaefer H, Krajka-Kuzniak V (1998) Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica 28:735–743

    Article  CAS  PubMed  Google Scholar 

  24. Krajka-Kuźniak V, Baer-Dubowska W (2003) The effects of tannic acid on cytochrome P450 and phase II enzyme in mouse liver and kidney. Toxicol Lett 143:209–216

    Article  PubMed  Google Scholar 

  25. Szaefer H, Jodynis-Liebert J, Cichocki M et al (2003) Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine. Toxicology 186:67–77

    Article  CAS  PubMed  Google Scholar 

  26. Ignatowicz E, Balana B, Vulimiri SV et al (2003) The effect of plant phenolics on the formation of 7,12-dimetylbenz[a]antracene-DNA adducts and TPA-stimulated polymorphonuclear neutrophils chemiluminescence in vitro. Toxicology 189:199–209

    Article  CAS  PubMed  Google Scholar 

  27. Gali HU, Perchellet EM, Perchellet JP (1991) Inhibition of tumor promoter induced ornithine decarboxylase activity by tannic acid and other polyphenols in mouse epidermis in vivo. Cancer Res 51:2820–2825

    CAS  PubMed  Google Scholar 

  28. Nafees S, Ahmad ST, Arjumand W et al (2013) Carvacrol ameliorates thioacetamide-induced hepatotoxicity by abrogation of oxidative stress, inflammation and apoptosis in liver of Wistar rats. Hum Exp Toxicol 32(12):1292–1304

    Article  CAS  PubMed  Google Scholar 

  29. Jollow DJ, Mitchell JR, Zampaglione N et al (1974) Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic intermediate. Pharmacology 11:151–169

    Article  CAS  PubMed  Google Scholar 

  30. Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods in oxygen radical research. CRC, Boca Raton, pp 283–284

    Google Scholar 

  31. Rashid S, Ali N, Nafees S et al (2013) Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicol Mech Methods 23(5):337–345

    Article  CAS  PubMed  Google Scholar 

  32. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  33. Carlberg I, Mannervik B (1975) Glutathione level in rat brain. J Biol Chem 250:5475–5480

    CAS  PubMed  Google Scholar 

  34. Nafees S, Ahmad ST, Arjumand W et al (2013) Hibiscus rosa sinensis alleviates thioacetamide induced acute hepatotoxicity in Wistar rats. Int J Drug Dev Res 5(1):1–10

    Google Scholar 

  35. Pick E, Keisari Y (1981) Superoxide anion and H2O2 production by chemically elicited peritoneal macrophages–induction by multiple non-phagocytic stimuli. Cell Immunol 59:301–308

    Article  CAS  PubMed  Google Scholar 

  36. Lowry OH, Rosebrough NJ, Farr A et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  37. Patel R, Krishnan R, Ramchandani A et al (2008) Polymeric black tea polyphenols inhibit mouse skin chemical carcinogenesis by decreasing cell proliferation. Cell Prolif 41:532–553

    Article  CAS  PubMed  Google Scholar 

  38. Athar M, Khan WA, Mukhtar H (1989) Effect of dietary tannic acid on epidermal, lung, and forestomach polycyclic aromatic hydrocarbon metabolism and tumorigenicity in Sencar mice. Cancer Res 49:5784–5788

    CAS  PubMed  Google Scholar 

  39. Gali HU, Perchellet EM, Klish DS et al (1992) Hydrolyzable tannins: potent inhibitors of hydroperoxide production and tumor promotion in mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate in vivo. Int J Cancer 51:425–432

    Article  CAS  PubMed  Google Scholar 

  40. Ahmad ST, Arjumand W, Seth A et al (2011) Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways. Toxicology 290:69–81

    Article  CAS  PubMed  Google Scholar 

  41. Rubin H (2001) Selected cell and selective microenvironment in neoplastic development. Cancer Res 61:799–807

    CAS  PubMed  Google Scholar 

  42. Nakamura Y, Kozuka M, Naniwa K et al (2003) Arachidonic acid cascade inhibitors modulate phorbol ester-induced oxidative stress in female ICR mouse skin: differential roles of 5-lipoxygenase and cyclooxygenase-2 in leukocyte infiltration and activation. Free Radic Biol Med 35:997–1007

    Article  CAS  PubMed  Google Scholar 

  43. Gerber M, Astre C, Segala C et al (1997) Tumor progression and oxidant–antioxidant status. Cancer Lett 114:211–214

    Article  CAS  PubMed  Google Scholar 

  44. Saintot M, Astre C, Pujol H (1996) Tumor progression and oxidant antioxidant status. Carcinogenesis 17:1267–1271

    Article  CAS  PubMed  Google Scholar 

  45. Sharma S, Sultana S (2004) Modulatory effect of soy isoflavones on biochemical alterations mediated by TPA in mouse skin model. Food Chem Toxicol 42:1669–1675

    Article  CAS  PubMed  Google Scholar 

  46. Tiwari M, Kakkar P (2009) Plant derived antioxidants—GOH and camphene protect rat alveolar macrophages against t-BHP induced oxidative stress. Toxicol Vitro 23:295–301

    Article  CAS  Google Scholar 

  47. Pillai CK, Pillai KS (2002) Antioxidants in health. Indian J Physiol Pharmacol 46:1–5

    CAS  PubMed  Google Scholar 

  48. Wei H, Wei L, Frenkel K et al (1993) Inhibition of tumour promoter induced hydrogen peroxide formation in vitro and in viva by genistein. Nutr Cancer 20:1–12

    Article  CAS  PubMed  Google Scholar 

  49. Stanley PL, Steiner S, Havens M et al (1991) Mouse skin inflammation induced by multiple topical applications of 12-O-tetradecanoylphorbol-13-acetate. Skin Pharmacol 4:262–271

    Article  CAS  PubMed  Google Scholar 

  50. Pence BC, Reiners JJ Jr (1987) Murine epidermal xanthine oxidase activity correlation with the hyperplasia induced by tumor promoter. Cancer Res 47:6388–6392

    CAS  PubMed  Google Scholar 

  51. Sun Y (1990) Free radicals, antioxidant enzymes and carcinogenesis. Free Rad Biol Med 8:5839

    Article  Google Scholar 

  52. Murakami A, NakamuraY Torikai K et al (2000) Inhibitory effect of citrus nobiletin on Phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res 60:5059–5066

    CAS  PubMed  Google Scholar 

  53. Slaga TJ (1984) Mechanisms involved in two-stage carcinogenesis in mouse skin. In: Slaga TJ (ed) Mechanisms of tumor promotion, vol 2. CRC Press, Boca Raton, pp 1–16

    Google Scholar 

  54. Kundu JK, Surh YJ (2008) Inflammation: gearing the journey to cancer. Mutat Res 659:15–30

    Article  CAS  PubMed  Google Scholar 

  55. Bravo R (1986) Synthesis of the nuclear protein cyclin (PCNA) and its relationship with DNA replication. Exp Cell Res 163:287–293

    Article  CAS  PubMed  Google Scholar 

  56. Bravo R, Frank R, Blundell PA et al (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 326:515–517

    Article  CAS  PubMed  Google Scholar 

  57. Jaskulski D, de Riel JK, Mercer WE et al (1988) Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. Science 240:15446

    Article  Google Scholar 

  58. Joseph LB, Gerecke DR, Heck DE et al (2011) Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage. Exp Mol Pathol 91:515–527

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Moore RJ, Owens DM, Stamp G et al (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 5:828–831

    Article  CAS  PubMed  Google Scholar 

  60. Tricot G (2000) New insights into role of microenvironment in multiple myeloma. Lancet 355:248–250

    Article  CAS  PubMed  Google Scholar 

  61. Vidal-Vanaclocha F, Fantuzzi G, Mendoza L et al (2000) IL-18 regulates IL-1 beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci USA 97:734–739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Smith CW, Chen Z, Dong G et al (1998) The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and KC. Clin Exp Metastasis 16:655–664

    Article  CAS  PubMed  Google Scholar 

  63. Philip M, Rowley DA, Schreiber H (2004) Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol l14:433–439

    Article  Google Scholar 

  64. Surh YJ, Chun KS, Cha HH et al (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and i-NOS through suppression of NF-κB activation. Mutat Res 480–481:243–268

    Article  PubMed  Google Scholar 

  65. Kim Y, Fischer SM (1998) Transcriptional regulation of cyclooxygenase-2 in mouse skin carcinoma cells. Regulatory role of CCAT/enhancer binding protein in the differential expression of cyclooxygenase-2 in normal and neoplastic tissues. J Biol Chem 273:27686–27694

    Article  CAS  PubMed  Google Scholar 

  66. Kundu JK, Shin YK, Kim SH et al (2006) Resveratrol inhibits phorbolester induced expression of COX-2 and activation of NF-κB in mouse skin by blocking IκB kinase activity. Carcinogenesis 27:1465–1474

    Article  CAS  PubMed  Google Scholar 

  67. Jenkins DC, Charles IG, Thomsen LL et al (1995) Roles of nitric oxide in tumor growth. Proc Natl Acad Sci USA 92:4392–4396

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Khan AQ, Khan R, Qamar W et al (2013) Geraniol attenuates 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammation in mouse skin: possible role of p38 MAP Kinase and NF-κB. Exp Mol Pathol 94:419–429

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Sarwat Sultana is thankful to Ministry of Higher Education Republic of Iraq to provide fellowship to one of the authors (Ms. Ferial Majed) to carry out this research work at Jamia Hamdard.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Ferial Majed, Summya Rashid, Abdul Quaiyoom Khan, Sana Nafees, Nemat Ali, Rashid Ali, Rehan Khan, Syed Kazim Hasan, Syed Jafar Mehdi & Sarwat Sultana

Authors
  1. Ferial Majed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Summya Rashid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdul Quaiyoom Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sana Nafees
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nemat Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rashid Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rehan Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Syed Kazim Hasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Syed Jafar Mehdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sarwat Sultana
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarwat Sultana.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Majed, F., Rashid, S., Khan, A.Q. et al. Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in mice. Mol Cell Biochem 399, 217–228 (2015). https://doi.org/10.1007/s11010-014-2248-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-014-2248-3

Keywords

Search

Navigation