Jagadeeshan, S and ManuPrasad, M. (2017) Nicotine mediated activation of Pak1/NFkB cascade in pancreatic cancer cells – A pilot study. New Horizons in Translational Medicine, 3 (6). pp. 284-288. ISSN 2307-5023

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Abstract

Background: Tobacco smoking is a major established risk factor for pancreatic cancer (PC), increasing the incidence up to six fold depending on the duration and intensity of smoking. Nicotine is a key toxin in tobacco and cigarette, which may contribute to development of pancreatitis and PC. Our previous studies revealed an aberrant expression of Pak1 in PC as compared to normal pancreas and its association with cancer progression, tumor angiogenesis, drug resistance and metastasis. Here, we explore a potential link between Pak1 expression and smoking-mediated PC pathogenesis and the use of Pak1 inhibitors to curtail this association. Methods: Mia Pa Ca 2 cell line was obtained from NCCS, Pune and grown in the presence and absence of 0.5 μM (0.112 μg/ml) nicotine hemisulphate salt (5 h) and further nicotine exposed cells were treated with Pak1 inhibitor, IPA-3 (1 h). Protein, mRNA and kinase activity of Pak1 were evaluated. Using human pancreatic cancer tissue, mRNA from smokers (n = 10) and non –smokers (n = 10) were assessed for Pak1 expression. Results: Nicotine significantly enhanced the expression and kinase activity of Pak1, with subsequent activation of NF-κB signalling cascade in cooperation with other pathways, this effect was blocked by IPA-3. Also, it was observed that pharmacological blockage or silencing of α7-nAChR abrogated nicotine mediated activation of Pak1/NF-κB. Additionally, we demonstrated up-regulated Pak1 mRNA expression in tissue sample from smokers compared to non-smokers. Conclusion: Our findings suggest probable mechanism of action of nicotine through Pak1 signalling on PC pathogenesis and this could be targeted using Pak1 inhibitors for PC treatment

Item Type:	Article
Uncontrolled Keywords:	Smoking Nicotine Pancreatic cancer Pak1 Inhibitor IPA-3
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	26 Apr 2018 08:13
Last Modified:	12 Apr 2019 07:55
URI:	http://rgcb.sciencecentral.in/id/eprint/566

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