Curcumin down regulates smokeless tobacco-induced NF-kappaB activation and COX-2 expression in human oral premalignant and cancer cells.
Smokeless tobacco (ST) consumption is a major cause of oral cancer in South East Asia including India. Recently, we showed that exposure to smokeless tobacco extract (STE) (khaini) results in increased expression and activation of nuclear factor-kappaB (NF-kappaB) and its downstream target cyclooxygenase-2 (COX-2) in human oral cell systems in vitro. The present study was designed to test the hypothesis that curcumin may inhibit the activation of NF-kappaB in ST exposed oral premalignant and cancer cells. Exposure of oral premalignant and cancer cells to curcumin resulted in significant decrease in cell viability and induced apoptosis. STE-induced nuclear translocation and DNA-binding activity of NF-kappaB were inhibited in curcumin pretreated oral premalignant and cancer cells in vitro. Curcumin treatment led to decreased expression of NF-kappaB and COX-2. The tobacco specific nitrosamine, 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK), is one of the carcinogenic components of STE (khaini). We demonstrate that curcumin pretreatment abrogated NNK-induced activation of NF-kappaB and COX-2 expression, suggesting that NNK is one of the factors in STE (khaini) modulated by curcumin. In conclusion, our findings demonstrate for the first time that curcumin downregulates STE (khaini) or NNK-induced NF-kappaB and COX-2 in oral premalignant and cancer cells in vitro.
Sharma
Chhavi
C
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Kaur
Jatinder
J
Shishodia
Shishir
S
Aggarwal
Bharat B
BB
Ralhan
Ranju
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D014030:Tobacco, Smokeless / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016328:NF-kappa B; D051546:Cyclooxygenase 2; D003474:Curcumin