Skip to main content
×
×
Home

Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways

  • Ila Das (a1), Asha Acharya (a2), Deborah L. Berry (a3), Supti Sen (a3), Elizabeth Williams (a3), Eva Permaul (a3), Archana Sengupta (a1), Sudin Bhattacharya (a1) and Tapas Saha (a3)...
Abstract

The role of dietary factors in inhibiting or delaying the development of non-melanoma skin cancer (NMSC) has been investigated for many years. Cardamom, which is a dietary phytoproduct, has been commonly used in cuisines for flavour and has numerous health benefits, such as improving digestion and stimulating metabolism and having antitumorigenic effects. We have investigated the efficacy of dietary cardamom against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomatogenesis in Swiss albino mice that closely resembles human NMSC. Mice were grouped into normal wild type (untreated), vehicle-treated (acetone), carcinogen-treated (DMBA), and DMBA and cardamom-treated (DMBA+CARD) to delineate the role of cardamom against DMBA-induced papillomatogenesis. Oral administration of cardamom to DMBA-treated mice up-regulated the phase II detoxification enzymes, such as glutathione-S-transferase and glutathione peroxidase, probably via activation of nuclear factor erythroid-2-related factor 2 transcription factor in ‘DMBA+CARD’ mice. Furthermore, reduced glutathione, glutathione reductase, superoxide dismutase and catalase were also up-regulated by cardamom in the same ‘DMBA+CARD’ group of mice compared with DMBA-treated mice. Cardamom ingestion in DMBA-treated mice blocked NF-κB activation and down-regulated cyclo-oxygenase-2 expression. As a consequence, both the size and the number of skin papillomas generated on the skin due to the DMBA treatment were reduced in the ‘DMBA+CARD’ group. Thus, the results from the present study suggest that cardamom has a potential to become a pivotal chemopreventive agent to prevent papillomagenesis on the skin.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Dr T. Saha, fax +1 202 687 5324, email ts283@georgetown.edu; tapassaha2000@gmail.com
References
Hide All
1National Cancer Institute Skin Cancer (2011) http://wwwcancergov/cancertopics/types/skin (accessed 22 September 2011).
2Ramos, J, Villa, J, Ruiz, A, et al. (2004) UV dose determines key characteristics of nonmelanoma skin cancer. Cancer Epidemiol Biomarkers Prev 13, 20062011.
3Acharya, A, Das, I, Chandhok, D, et al. (2010) Redox regulation in cancer: a double-edged sword with therapeutic potential. Oxid Med Cell Longev 3, 2334.
4Sander, CS, Hamm, F, Elsner, P, et al. (2003) Oxidative stress in malignant melanoma and non-melanoma skin cancer. Br J Dermatol 148, 913922.
5Sporn, MB, Dunlop, NM, Newton, DL, et al. (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 35, 13321338.
6Tapsell, LC, Hemphill, I, Cobiac, L, et al. (2006) Health benefits of herbs and spices: the past, the present, the future. Med J Aust 185, S424.
7Wikipedia TFE (2011) Cardamom. Wikimedia Foundation, Inc. (cited 16 September 2011).
8Zachariah, TJ Chemistry of cardamom. In Cardamom, The Genus Elettaria [Ravindran, PM and Madhusoodanan, KJ, editors]. London: Taylor and Francis.
9Acharya, A, Das, I, Singh, S, et al. (2010) Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric 2, 166177.
10Huang, YB, Fang, JY, Hung, CH, et al. (1999) Cyclic monoterpene extract from cardamom oil as a skin permeation enhancer for indomethacin: in vitro and in vivo studies. Biol Pharm Bull 22, 642646.
11Bhattacharjee, S, Rana, T & Sengupta, A (2007) Inhibition of lipid peroxidation and enhancement of GST activity by cardamom and cinnamon during chemically induced colon carcinogenesis in Swiss albino mice. Asian Pac J Cancer Prev 8, 578582.
12Das, I & Saha, T (2009) Effect of garlic on lipid peroxidation and antioxidation enzymes in DMBA-induced skin carcinoma. Nutrition 25, 459471.
13Ando, S, Kon, K, Aino, K, et al. (1990) Increased levels of lipid peroxides in aged rat brain as revealed by direct assay of peroxide values. Neurosci Lett 113, 199204.
14Habig, WH, Pabst, MJ & Jakoby, WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249, 71307139.
15Paglia, DE & Valentine, WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70, 158169.
16Luck, H (1963) A spectrophotometric method for the measurement of catalase. Meth Enzymatic Anal 27, 885895.
17Marklund, 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, 469474.
18Sedlak, J & Lindsay, RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 25, 192205.
19Carberg, I & Mannervick, B (1985) Glutathione reductase. In Methods in Enzymology [Fleisher, S and Packer, L, editors]. New York, NY: Academic Press.
20Das, I, Das, S & Saha, T (2009) Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: a histopathological study. Acta Histochem 26, 26.
21Cho, HY, Reddy, SP, Debiase, A, et al. (2005) Gene expression profiling of NRF2-mediated protection against oxidative injury. Free Radic Biol Med 38, 325343.
22Kensler, TW & Wakabayashi, N (2009) Nrf2: friend or foe for chemoprevention? Carcinogenesis 30, 30.
23Motohashi, H & Yamamoto, M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10, 549557.
24Baud, V & Karin, M (2009) Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8, 3340.
25Zandi, E, Rothwarf, DM, Delhase, M, et al. (1997) The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 91, 243252.
26Sochanowicz, B, Szumiel, I & Gradzka, I (1999) Nuclear translocation of the p65 subunit of NF-kappaB in L5178Y sublines differing in antioxidant defense. Radiat Environ Biophys 38, 125131.
27Miglietta, A, Toselli, M, Ravarino, N, et al. (2010) COX-2 expression in human breast carcinomas: correlation with clinicopathological features and prognostic molecular markers. Expert Opin Ther Targets 14, 655664.
28An, KP, Athar, M, Tang, X, et al. (2002) Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches. Photochem Photobiol 76, 7380.
29Surh, YJ (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3, 768780.
30Katiyar, SK & Mukhtar, H (2001) Green tea polyphenol ( − )-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress. J Leukoc Biol 69, 719726.
31Wei, H, Zhang, X, Wang, Y, et al. (2002) Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein. Cancer Lett 185, 2129.
32Wang, Y, Zhang, X, Lebwohl, M, et al. (1998) Inhibition of ultraviolet B (UVB)-induced c-fos and c-jun expression in vivo by a tyrosine kinase inhibitor genistein. Carcinogenesis 19, 649654.
33Afaq, F, Adhami, VM & Ahmad, N (2003) Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice. Toxicol Appl Pharmacol 186, 2837.
34Adhami, VM, Afaq, F & Ahmad, N (2003) Suppression of ultraviolet B exposure-mediated activation of NF-kappaB in normal human keratinocytes by resveratrol. Neoplasia 5, 7482.
35Katiyar, SK, Korman, NJ, Mukhtar, H, et al. (1997) Protective effects of silymarin against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst 89, 556566.
36Cho, JW, Park, K, Kweon, GR, et al. (2005) Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets. Exp Mol Med 37, 186192.
37Kim, JK, Kim, Y, Na, KM, et al. (2007) [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo. Free Radic Res 41, 603614.
38Fazekas, Z, Gao, D, Saladi, RN, et al. (2003) Protective effects of lycopene against ultraviolet B-induced photodamage. Nutr Cancer 47, 181187.
39Kowalczyk, MC, Kowalczyk, P, Tolstykh, O, et al. (2010) Synergistic effects of combined phytochemicals and skin cancer prevention in SENCAR mice. Cancer Prev Res 3, 170178.
40Bowden, GT, Schneider, B, Domann, R, et al. (1994) Oncogene activation and tumor suppressor gene inactivation during multistage mouse skin carcinogenesis. Cancer Res 54, 1882s1885s.
41Kapadia, GJ, Azuine, MA, Sridhar, R, et al. (2003) Chemoprevention of DMBA-induced UV-B promoted, NOR-1-induced TPA promoted skin carcinogenesis, and DEN-induced phenobarbital promoted liver tumors in mice by extract of beetroot. Pharmacol Res 47, 141148.
42Kim, MO, Kim, SH, Shin, MJ, et al. (2007) DMBA/TPA-induced tumor formation is aggravated in human papillomavirus type 16 E6/E7 transgenic mouse skin. Oncol Res 16, 325332.
43Schneider, BL, Bowden, GT, Sutter, C, et al. (1993) 7,12-Dimethylbenz[a]anthracene-induced mouse keratinocyte malignant transformation independent of Harvey ras activation. J Invest Dermatol 101, 595599.
44Bhattacharyya, SS, Paul, S, Mandal, SK, et al. (2009) A synthetic coumarin (4-methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice. Eur J Pharmacol 614, 128136.
45Chaudhary, SC, Alam, MS, Siddiqui, MS, et al. (2009) Chemopreventive effect of farnesol on DMBA/TPA-induced skin tumorigenesis: involvement of inflammation. Ras-ERK pathway and apoptosis. Life Sci 85, 196205.
46Bartsch, H & Nair, J (2005) Accumulation of lipid peroxidation-derived DNA lesions: potential lead markers for chemoprevention of inflammation-driven malignancies. Mutat Res 591, 3444.
47Hayes, JD & McMahon, M (2009) NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci 34, 176188.
48Wang, R, An, J, Ji, F, et al. (2008) Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem Biophys Res Commun 373, 151154.
49Ulivi, V, Giannoni, P, Gentili, C, et al. (2008) p38/NF-kB-dependent expression of COX-2 during differentiation and inflammatory response of chondrocytes. J Cell Biochem 104, 13931406.
50Kim, HJ, Hawke, N & Baldwin, AS (2006) NF-kappaB and IKK as therapeutic targets in cancer. Cell Death Differ 13, 738747.
51Perkins, ND & Gilmore, TD (2006) Good cop, bad cop: the different faces of NF-kappaB. Cell Death Differ 13, 759772.
52Kobielak, A & Fuchs, E (2006) Links between alpha-catenin, NF-kappaB, and squamous cell carcinoma in skin. Proc Natl Acad Sci U S A 103, 23222327.
53Huang, S, DeGuzman, A, Bucana, CD, et al. (2000) Level of interleukin-8 expression by metastatic human melanoma cells directly correlates with constitutive NF-kappaB activity. Cytokines Cell Mol Ther 6, 917.
54Payne, AS & Cornelius, LA (2002) The role of chemokines in melanoma tumor growth and metastasis. J Invest Dermatol 118, 915922.
55Richmond, A (2002) Nf-kappa B, chemokine gene transcription and tumour growth. Nat Rev Immunol 2, 664674.
56Li, JJ, Rhim, JS, Schlegel, R, et al. (1998) Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes. Oncogene 16, 27112721.
57Dajee, M, Lazarov, M, Zhang, JY, et al. (2003) NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 421, 639643.
58Saleem, M, Afaq, F, Adhami, VM, et al. (2004) Lupeol modulates NF-kappaB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice. Oncogene 23, 52035214.
59Arora, N, Bansal, MP & Koul, A (2011) Azadirachta indica exerts chemopreventive action against murine skin cancer: studies on histopathological, ultrastructural changes and modulation of NF-kappaB, AP-1, and STAT1. Oncol Res 19, 179191.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Type Description Title
PDF
Supplementary materials

Das supplementary material
Das supplementary material

 PDF (664 KB)
664 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed