Effects of a natural polyphenol on nicotine-induced pancreatic cancer cell proliferation

Abstract

INTRODUCTION Resveratrol ( trans -3, 4’, 5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits, has anti-inflammatory and anti-oxidant effects. Its anti-carcinogenic effects are closely associated with its antioxidant activity; thus, the use of resveratrol as a possible cancer chemo-preventive is considered to be an important area of investigation. In this study we have examined the inhibitory effects of resveratrol in nicotine induced proliferation of pancreatic cancer cells. METHODS Cultured AR42J cells were incubated with 100 μM nicotine for 3 min and with 100 μM resveratrol for 30 min, either alone or in combination. Proliferation assays were conducted for a period of 0 to 96 h in serum media, incubated with nicotine and resveratrol, and evaluated by MTT assay. Protein was measured in lysed cells and activation of MAPK signals was measured by western blot using purified p-ERK antibody. Co-localization of activated ERK signals was confirmed by FITC conjugated ERK antibody using immunofluorescence assay and confocal microscopy. Biomarker of lipid peroxidation was determined in cell lysates by malondialdehyde (MDA) bioassay. RESULTS Resveratrol significantly suppressed the nicotine-induced proliferation of acinar cells compared to untreated controls (p<0.05). Mitogen activated protein kinase (MAPK) analysis revealed up-regulation of p-ERK expression by nicotine (p<0.05) that was suppressed significantly by resveratrol (p<0.05). Co-localization of activated ERK signals was confirmed by FITC conjugated ERK antibody, and this response was reduced significantly by resveratrol. Nicotine-induced malondialdehyde formation was also suppressed by resveratrol (p<0.05). CONCLUSIONS The data suggest that resveratrol suppressed nicotine-induced AR42J cell proliferation. The proliferation of AR42J cells by nicotine is associated with activation of MAPK signals and induction of protein oxidation. Resveratrol suppressed lipid peroxidation and P-ERK activated signals induced by nicotine. We conclude that resveratrol acts as an effective antioxidant in reversing the nicotine induced pancreatic cancer cell proliferation.

Nicotine has no significant cytoprotective activity against SARS-CoV-2 infection

“…To test whether nicotine was active in the cell growth media and cell culture condition using the DMEM supplemented with 2 mM L-glutamine, we treated A549 lung cancer cells with the nicotine (2 or 10 μM) or the vehicle control (0 μM nicotine) for 48 hours. It has been reported that nicotine can activate the Erk in multiple cell lines via promotion of the Erk phosphorylation [40][41][42][43][44][45]. We found that nicotine indeed induced Erk1/2 phosphorylation in A549 cells as shown in Fig 2 , suggesting that nicotine was active in the cell culture media DMEM supplemented with 2 mM L-glutamine.…”

Complex interactions between nicotine and resveratrol in the Drosophila melanogaster wing spot test

“…RES has been attributed multiple beneficial properties such as being an antioxidant, a free radical scavenger and increasing longevity [ 32 , 33 , 41 , 74 ]. However, very few studies have examined if RES could modulate the effects of NIC [ 49 – 51 ]. Moreover, the effect of RES on the putative genotoxic effect of NIC has not been studied in vivo .…”

“…Only a few in vitro studies have examined whether NIC’s effects could be modulated by RES. There is evidence that RES can protect against NIC-induced oxidative damage in renal tubule cells [ 49 ] Leydig cells [ 50 ], and against NIC-induced proliferation of pancreatic cells [ 51 ]. A couple in vivo studies in rats showed that RES reduces NIC-induced changes in the lungs [ 52 ], and NIC-induced renal impairment after chronic NIC exposure [ 53 ].…”

Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways

“…Nicotine represents the most toxic factor of tobacco, may lead to excessive cell proliferation through an increase in oxidative stress, and also has been related to an improvement of the invasiveness of lung and breast cancer cells ( Bose et al, 2005 ; Dasgupta et al, 2009 ). Resveratrol prevents nicotine-induced cell proliferation through the MAPK signaling pathway by means of the downregulation of p-ERK in pancreatic cells ( Chowdhury et al, 2018a ). Alcohol consumption has been related to the development of colorectal cancer ( Nishihara et al, 2014 ).…”