Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG
Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG
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DOI：
10.1007/s10637-009-9345-2
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发表时间：
2011-02-01
影响因子：
3.4
通讯作者：
Nagini, S.
中科院分区：
文献类型：
--
作者：
Manikandan, P.;Vinothini, G.;Nagini, S.
The modulation of intracellular nuclear factor-kappaB (NF-kappa B) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is known to possess attractive remedial features. In the present study, we investigated the modulatory effects of eugenol on NF-kappa B signaling in a rat model of gastric carcinogenesis induced by N-methyl-N-'-nitro-N-nitrosoguanidine (MNNG) by analysing the expression of nuclear factor-kappaB (NF-kappa B) family members ((NF-kappa B (p50 and p65), inhibitor of kappaB alpha (I kappa B alpha), phosphorylated I kappa B alpha (p-I kappa B alpha), I kappa B kinase beta (IKK beta)) and the NF-kappa B target genes that promote (e.g., cyclin D1, cyclin B and PCNA) or inhibit (e.g., p53, p21, and Gadd45) cell proliferation and cell survival. MNNG-induced gastric tumours were characterized by NF-kappa B activation that correlated with upregulation of IKK beta, and phosphorylation and degradation of I kappa B alpha. Furthermore, upregulation of cyclins and PCNA with downregulation of p21, p53, and Gadd45 suggested that the proliferative advantage in gastric carcinomas is dependent on elevated constitutive NF-kappa B activity. Administration of eugenol significantly reduced the incidence of MNNG-induced gastric tumours by suppressing NF-kappa B activation and modulating the expression of NF-kappa B target genes that regulate cell proliferation and cell survival. The targeting of NF-kappa B signaling pathway by eugenol may have a significant impact on chemopreventive and therapeutic approaches for cancer.
