Expression of NF‐κB parallels COX‐2 expression in oral precancer and cancer: Association with smokeless tobacco

Abstract

Nuclear Factor‐κB (NF‐κB) activation and COX‐2 overexpression have been reported in head and neck cancer, but the relationship between these proteins remains to be investigated. To determine the relationship between NF‐κB and COX‐2 in Smokeless Tobacco (ST) associated oral tumorigenesis, we performed immunohistochemistry in serial sections from 107 OSCCs, 78 oral precancerous lesions (OPLs) (58 hyperplasias, 20 dysplasias) and 15 histologically normal oral tissues and correlated with clinicopathological data. Significant increase in NF‐κB and COX‐2 immunopositivity was observed from normal oral mucosa to OPLs to OSCCs (p = 0.009 and p = 0.002 respectively). Upregulation of NF‐κB and COX‐2 was observed as early as in hyperplasia [p = 0.006; OR = 6.1 and p = 0.003; OR = 7.6, respectively]. Expression of both proteins was found to be significantly associated in OPLs (p = 0.000; OR = 12.6) and OSCCs (p = 0.001; OR = 4.0). Intriguingly, khaini consumption correlated with NF‐κB immunopositivity in OPLs (p = 0.05, OR = 3.8) and OSCCs (p = 0.01, OR = 3.4) and with COX‐2 expression in OPLs (p = 0.03; OR = 4.3). In vitro experimental system of ST associated oral carcinogenesis was used to demonstrate ST (khaini) and NNK mediated activation of NF‐κB and COX‐2, supporting the clinical data. In conclusion, this study demonstrates correlation between over expression of NF‐κB and COX‐2 in early precancerous stages of development of oral cancer and sustained elevation down the tumorigenic pathway, underscoring their potential as targets for early intervention. In vitro studies demonstrated that NNK may be one of the carcinogenic components of ST (khaini) inducing activation of NF‐κB and COX‐2 in oral precancer and cancer cells, suggesting plausible role in ST‐induced oral carcinogenesis. © 2007 Wiley‐Liss, Inc.

Pharmacological Importance of Simple Phenolic Compounds on Inflammation, Cell Proliferation and Apoptosis with a Special Reference to β-D-Salicin and Hydroxybenzoic Acid

“…3, the activation of NF-KB contributes to the transcriptional activation of COX-2. Given that the over expression of both of these molecules has been noted in pre-cancerous and cancer cells (37), it provides a rationale for developing new chemotherapeutic or chemopreventative agents targeting their expression of function. In this regard, 2-HBA [3] and 2-HBNa induce significant anti-inflammatory effects in human umbilical vein endothelial cells and foreskin fibroblasts by inhibited COX-2 transcription in a concentration-dependent manner, thereby reducing the synthesis of proinflammatory prostaglandins (5).…”

Haem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis

“…Activation of NF-kB and MAPK in NNK-treated NCI-H23 cells NF-kB is constitutively activated in several types of cancer cells [15,16]. In addition, previous studies have shown that NNK activates NF-kB in macrophages [26] and that NF-kB is involved in the growth of colon cancer and oral cancer cells [27,28]. However, few studies have addressed the relationship between NNK and NF-kB in lung cancer.…”

Up-regulation of Inflammatory Signalings by Areca Nut Extract and Role ofCyclooxygenase-2−1195G>A Polymorphism Reveal Risk of Oral Cancer

“…The elevated COX-2 expression is well recognized as having a potential role in contributing to the progress of head and neck cancer through several biological pathways (7)(8)(9). The 5 ¶-coding sequence of the COX-2 gene contains an epidermal growth factor (EGF)-like domain.…”