Abstract
BackgroundCompounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events.MethodsHuman NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53.ResultsIn A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells.ConclusionsRed wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further systematic investigation in animal models of lung cancer.
Highlights
Cancer cells are characterized by accelerated proliferative capacity and resistance to apoptosis
In the present study we found a significant inhibition of human lung cancer cell proliferation and survival, inhibition of Akt and extracellular signal-regulated kinase (Erk) and induction of p53 by wine
Assuming that the resveratrol (MW:228.24 g/mol) concentration in our wine was 5 mg/L it is calculated that at the highest wine concentration (5%) used in our study, the cells would have been exposed to 1.1 μM resveratrol and we used this concentration of resveratrol and examined cell proliferation
Summary
Cancer cells are characterized by accelerated proliferative capacity and resistance to apoptosis (programmed cell death). Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and despite utilization of aggressive radio- and/or chemotherapy, fewer than 20% of such patients reach a 5 year survival [1]. This is due to significant resistance of NSCLC to such conventional cytotoxic therapies. There is an urgent need to Molecular signaling pathways of growth factor receptors, such as the Epidermal Growth Factor (EGF) Receptor (EGFR), stimulate cancer cell growth, survival and resistance to cytotoxic therapy. We examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events
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