Suppression of phorbol ester-induced nf-κB activation by capsaicin in cultured human promyelocytic leukemia cells
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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 wordsActivator protein-1 (AP-1) Capsaicin HL-60 cells NF-κB TPA
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- Chabot-Fletcher, M., Transcription factor NF-κB: an emerging anti-inflammatory drug target.Pharmacol. Rev. Commun., 8, 317–324 (1996).Google Scholar
- 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
- 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
- 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
- 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
- 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