Suppression of phorbol ester-induced NF-kappaB activation by capsaicin in cultured human promyelocytic leukemia cells.
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-kappaB 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-kappaB through inhibition of IkappaB alpha 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-kappaB DNA binding. Likewise, TPA-induced activation of AP-1 was mitigated by capsaicin treatment.
Han
Seong-Su
SS
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Korea.
Keum
Young-Sam
YS
Chun
Kyung-Soo
KS
Surh
Young-Joon
YJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D002467:Cell Nucleus / Q000737:chemistry; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis / Q000235:genetics; D010703:Phorbol Esters / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D016759:Oncogene Protein p65(gag-jun); D010703:Phorbol Esters; D018808:Transcription Factor AP-1; D004247:DNA; D002211:Capsaicin