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Archives of Pharmacal Research

, Volume 25, Issue 4, pp 475–479 | Cite as

Suppression of phorbol ester-induced nf-κB activation by capsaicin in cultured human promyelocytic leukemia cells

  • Seong-Su Han
  • Young-Sam Keum
  • Kyung-Soo Chun
  • Young-Joon Surh
Research Articles Articles

Abstract

Capsaicin, a major pungent constituent of red pepper (Capsicum annuum L.) possesses a vast variety of pharmacologic and physiologic activities. Despite its irritant properties, the compound exerts anti-inflammatory and anti-nociceptive effects. Previous studies from this laboratory revealed that capsaicin, when topically applied onto dorsal skin of female ICR mice, strongly attenuated activation of NF-κB and AP-1 induced by the typical tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), which may account for its anti-tumor promoting activity in mouse skin. In the present work, we have found that capsaicin suppresses TPA-stimulated activation of NF-κB through inhibition of IκBα degradation and blockade of subsequent nuclear translocation of p65 in human promyelocytic leukemia HL-60 cells. Methylation of the phenolic hydroxyl group of capsaicin abolished its inhibitory effect on NF-κB DNA binding. Likewise, TPA-induced activation of AP-1 was mitigated by capsaicin treatment.

Key words

Activator protein-1 (AP-1) Capsaicin HL-60 cells NF-κB TPA 

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References

  1. Abate, C., Patel, F. J., Rauscher, T. III and Curran, T., Redox regulation of fos and jun DNA-binding activtyin vitro.Science, 249, 1157–1161 (1990).PubMedCrossRefGoogle Scholar
  2. Angel, P., and Karin, M., The role of Jun, Fos and the AP-1 complex in cell proliferation and transformation.Biochim. Biophys. Acta, 1072, 129–157 (1991).PubMedGoogle Scholar
  3. Baeuerle, PA, IkappaB-NF-kappaB structures: at the interface of inflammation control.Cell, 95, 729–731 (1998).PubMedCrossRefGoogle Scholar
  4. Baeuerle, P.A. and Baltimore, D., NF-kappaB: ten years after.Cell, 87, 13–20 (1996).PubMedCrossRefGoogle Scholar
  5. Barnes, P. and Karin, M., Nuclear factor-κB-a pivotal transcription factor in chronic inflammatory diseases.N. Eng. J. Med., 336, 1066–1071 (1997).CrossRefGoogle Scholar
  6. Brar, S.S., Kennedy, T.P., Whorton, A.R., Sturrock, A.B., Huecksteadt, T.P., Ghio, A.J. and Hoidal, J.R., Reactive oxygen species from NAD(P)H:quinone oxidoreductase constitutively activate NF-κB in malignant melanoma cells.Am. J. Physiol. Cell Physiol., 280, C659-C676 (2001).PubMedGoogle Scholar
  7. Chabot-Fletcher, M., Transcription factor NF-κB: an emerging anti-inflammatory drug target.Pharmacol. Rev. Commun., 8, 317–324 (1996).Google Scholar
  8. De, A.K. and Ghosh, J.J., Studies on capsaicin inhibition of chemically-induced lipid peroxidation in the lung and liver tissues of rat.Phytother. Res., 6, 34–37 (1992).CrossRefGoogle Scholar
  9. Han, S.S., Keum, Y.-S., Seo, H.-J. and Surh, Y.-J., Curcumin suppresses activation of NF-κB and AP-1 induced by phorbol ester in cultured human promyelocytic leukemia (HL-60) cells.J. Biochem. Mol. Biol., 35, 337–342 (2002).PubMedGoogle Scholar
  10. Han, S.S., Keum, Y.-S., Seo, H.-J., Chun, K.-S., Lee, S.S. and Surh, Y.-J., Capsaicin suppresses phorbol ester-induced activation of NF-κB/Rel and AP-1 transcription factors in mouse epidermis.Cancer Lett., 164, 119–126 (2001).PubMedCrossRefGoogle Scholar
  11. Harvey, J.S., Davis, C., James, I.F. and Burgess, G.M., Activation of protein kinase C by the capsaicin analogue resiniferatoxin in sensory neurons.J. Neurochem., 65, 1309–1317 (1995).PubMedCrossRefGoogle Scholar
  12. Janusz, J.M., Buckwalter, P.A., Young, P.A., LaHann, T.R., Farmer, R.W., Kasting, G.B., Loomans, M.E., Kerckacrt, G.A., Maddin, C.S., Berman, E.F., Bohne, R.L., Cupps, T.L. and Milstein, J.R., Vanilloids. 1. Analogs of capsaicin with antinociceptive and anti-inflammatory activity.J. Med. Chem., 36, 2595–2604 (1993).PubMedCrossRefGoogle Scholar
  13. Joe, B. and Lokesh, B.R., Role of capsaicin, curcumin, and dietary n-3 fatty acids lowering the generation of reactive oxygen species in rat peritoneal macrophages.Biochim. Biophys. Acta, 1224, 255–263 (1994).PubMedCrossRefGoogle Scholar
  14. Jung, M.Y., Kang, H.J. and Moon, A., Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 down-regulation and caspase-3 activation.Cancer Lett., 165, 139–145 (2001).PubMedCrossRefGoogle Scholar
  15. Kim, J.-D., Kim, J.-M., Pyo, J.-O., Kim, S.-Y., Kim, B.-S., Yu, R. and Han, l.-S., Capsaicin can alter the expression of tumor forming-related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line, SNU-1.Cancer Lett., 120, 235–241 (1997).PubMedCrossRefGoogle Scholar
  16. Kong, A.-N. T., Yu, R., Chen, C., Mandlekar, S. and Primiano, T., Signal transduction events elicited by natural products.Arch. Pharm. Res., 23, 1–16 (2000).PubMedCrossRefGoogle Scholar
  17. Lee, Y.S., Nam, D.H. and Kim, J.A., Induction of apoptosis by capsaicin in A172 human glioma cells.Cancer Lett., 161, 121–130 (2000).PubMedCrossRefGoogle Scholar
  18. Morré, D.J., Chueh, P.J. and Morré, D.M., Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture.Proc. Natl. Acad. Sci. USA, 92, 1831–1835 (1995).PubMedCrossRefGoogle Scholar
  19. Morré, D.J., Sun, E., Geilen, C., Wu, L.Y., de Cabo, R., Krasagakis, K., Orfanos, C.E. and Morre, D.M., Capsaicin inhibits plasma membrane NADH oxidase and growth of human and mouse melanoma lines.Eur. J. Cancer, 32A, 1995–2003 (1996).PubMedCrossRefGoogle Scholar
  20. Macho, A., Blàzquez, M.-V., Navas, P. and Muñoz, E., Induction of apoptosis by vanilloid compounds does not requirede novo gene transcription and activator protein 1 activity.Cell Growth Differ, 9, 277–286 (1998).PubMedGoogle Scholar
  21. Macho, A., Calzado, M.A., Munoz-Blanco, J., Gomez-Diaz, C., Gajate, C., Mollinedo, F., Navas, P. and Muñoz, E., Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium.Cell Death Differ, 6, 155–165 (1999).PubMedCrossRefGoogle Scholar
  22. Morré, D.J., Chueh, P.J. and Morré, D.M., Capsaicin inhibits preferentially the NADPH oxidase and growth of transformed cells in culture.Proc. Natl. Acad. Sci. USA, 92, 1831–1835 (1995).PubMedCrossRefGoogle Scholar
  23. Morré, D.J., Sun, E., Geilen, C., Wu, L.Y., de Cabo, R., Krasagakis, K., Orfanos, C.E. and Morré, D.M., Capsaicin inhibits plasma membrane NADH oxidase and growth of human and mouse melanoma cell line.Eur. J. Cancer, 32A, 1995–2003 (1996).PubMedCrossRefGoogle Scholar
  24. Park, K.-K., Chun, K.-S., Yook, J. I., and Surh, Y- J., Lack of tumor promoting activity of capsaicin, a principal pungent ingredient of red pepper, in mouse skin carcinogenesis.Anticancer Res., 18, 4201–4206 (1998).PubMedGoogle Scholar
  25. Reddy, A.Ch. and Lokesh, B.R., Studies on anti-inflammatory activity of apice principles and dietary n-3 polyunsaturated fatty acids on carageenan-induced inflammation in rats.Ann. Nutr. Metab., 38, 349–358 (1994).PubMedCrossRefGoogle Scholar
  26. Savitha, G. and Salimath, B.P., Effects of capsaicin on phospholipase A2 activity and superoxide generation in macrophages.Nutr. Res., 15, 1417–1427 (1995).CrossRefGoogle Scholar
  27. Santoni, G., Perfumi, M.C., Pompei, P., Spreghini, E., Lucciarini, R., Martarelli, D., Staffolani, M. and Piccoli, M., Impairment of rat thymocyte differentiation and functions by neonatal capsaicin treatment is associated with induction of apoptosis.J. Neuroimmunol., 104, 37–46 (2000).PubMedCrossRefGoogle Scholar
  28. Sen, C. K. and Packer, L. Antioxidant and redox regulation of gene transcription.FASEB J., 10, 709–720 (1996).PubMedGoogle Scholar
  29. Singh, S., Natarajan, K. and Aggarwal, B.B., Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a potent inhibitor of nuclear transcription factor-κB activation by diverse agents.J. Immunol., 157, 4412–4420 (1996).PubMedGoogle Scholar
  30. Surh, Y.-J., Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances.Mutat. Res., 428, 305–327 (1999).PubMedGoogle Scholar
  31. Surh, Y.-J., Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review.Food Chem. Toxicol., 40, 1091–1097 (2002).PubMedCrossRefGoogle Scholar
  32. Surh, Y.-J., Chun, K.-S., Cha, H.-H., Han, S.S., Keum, Y.-S., Park, K.-K. and Lee, S.S., Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation.Mutat. Res., 480-481, 243–268 (2001).PubMedGoogle Scholar
  33. Surh, Y.-J., Lee, E. and Lee, J.M., Chemoprotective properties of some pungent ingredients presence in red pepper and ginger.Mutat. Res., 402, 259–267 (1997).Google Scholar
  34. Surh, Y.-J. and Lee, S.S., Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential.Life Sci., 56, 1845–1855 (1995).PubMedCrossRefGoogle Scholar
  35. Surh, Y.-J. and Lee, S.S., Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen?Food Chem. Toxicol., 34, 313–316 (1996).PubMedCrossRefGoogle Scholar
  36. Szallasi, A. and Blumberg, P.M. Vanilloid (capsaicin) receptors and mechanisms.Pharmacol. Rev., 51, 159–211 (1999).PubMedGoogle Scholar
  37. Thanos, D. and Maniatis, T. (1995) NF-κB: a lesson in family values.Cell, 80, 529–532.PubMedCrossRefGoogle Scholar
  38. Wang, J.-P., Hsu, M.-F, Hsu, T.-P. and Teng, C.-M., Antihemostatic and antithrombotic effects of capsaicin in comparison with aspirin and indomethacin.Thromb. Res., 37, 669–679 (1985).PubMedCrossRefGoogle Scholar
  39. Wolvetang, E.J., Larm, J.A., Moutsoulas, P. and Lawen, A., Apoptosis induced by inhibitors of the plasma membrane NADH-oxidase involves Bcl-2 and calcineurin.Cell Growth Differ, 7, 1315–1325 (1996).PubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2002

Authors and Affiliations

  • Seong-Su Han
    • 1
  • Young-Sam Keum
    • 1
  • Kyung-Soo Chun
    • 1
  • Young-Joon Surh
    • 1
  1. 1.Research Institute of Pharmaceutical Sciences, College of PharmacySeoul National UniversitySeoulKorea

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