Inhibition of human lung cancer cell proliferation and survival by wine

Cancer Cell International

Evangelia Tsiani¹  Gary Pickering²  Theodoros Tsakiridis³  Jessy Moore¹  Carly C Barron¹ 

[1] Department of Health Sciences, Brock University, St. Catharines, Ontario L2S 3A1, Canada;Department of Biological Sciences, Cool Climate Oenology and Viticulture Institute (CCOVI), Brock University, St. Catharines, Ontario L2S 3A1, Canada;Department of Oncology, McMaster University, Hamilton, Ontario L8S 4L8, Canada

关键词: Wine;    p53;    Erk;    Akt;    Survival;    Proliferation;    Cancer;   

Others  :  792436
DOI  :  10.1186/1475-2867-14-6

 received in 2013-07-04, accepted in 2014-01-16,  发布年份 2014

【 摘 要 】

Background

Compounds 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.

Methods

Human 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.

Results

In 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.

Conclusions

Red 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.

【 授权许可】

   
2014 Barron et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Navada S, Lai P, Schwartz A, Kalemkerian G: Temporal trends in small cell lung cancer: analysis of the National Surveillance, Epidemiology, and End-Results (SEER) database. J Clin Oncol 2006, 24(18):384S-384S.
• [2]Mitsudomi T, Yatabe Y: Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 2010, 277(2):301-308.
• [3]Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005, 2(3):e73.
• [4]Manning BD, Cantley LC: AKT/PKB signaling: navigating downstream. Cell 2007, 129(7):1261-1274.
• [5]Liu P, Cheng H, Roberts TM, Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009, 8(8):627-644.
• [6]Brognard J, Clark AS, Ni Y, Dennis PA: Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res 2001, 61(10):3986-3997.
• [7]Tang J, He Q, Guo R, Chang X: Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer 2006, 51(2):181-191.
• [8]Lee SH, Kim HS, Park WS, Kim SY, Lee KY, Kim SH, Lee JY, Yoo NJ: Non-small cell lung cancers frequently express phosphorylated Akt; an immunohistochemical study. APMIS 2002, 110(7–8):587-592.
• [9]Roberts PJ, Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007, 26(22):3291-3310.
• [10]Chen F, Wang W, El-Deiry WS: Current strategies to target p53 in cancer. Biochem Pharmacol 2010, 80(5):724-730.
• [11]German JB, Walzem RL: The health benefits of wine. Annu Rev Nutr 2000, 20:561-593.
• [12]Elattar TM, Virji AS: The effect of red wine and its components on growth and proliferation of human oral squamous carcinoma cells. Anticancer Res 1999, 19(6B):5407-5414.
• [13]Wallenborg K, Vlachos P, Eriksson S, Huijbregts L, Arner E, Joseph B, Hermanson O: Red wine triggers cell death and thioredoxin reductase inhibition: Effects beyond resveratrol and SIRT1. Exp Cell Res 2009, 315(8):1360-1371.
• [14]Kampa M, Hatzoglou A, Notas G, Damianaki A, Bakogeorgou E, Gemetzi C, Kouroumalis E, Martin PM, Castanas E: Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines. Nutr Cancer 2000, 37(2):223-233.
• [15]Damianaki A, Bakogeorgou E, Kampa M, Notas G, Hatzoglou A, Panagiotou S, Gemetzi C, Kouroumalis E, Martin PM, Castanas E: Potent inhibitory action of red wine polyphenols on human breast cancer cells. J Cell Biochem 2000, 78(3):429-441.
• [16]Baur J, Sinclair D: Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006, 5(6):493-506.
• [17]Rashid A, Liu C, Sanli T, Tsiani E, Singh G, Bristow RG, Dayes I, Lukka H, Wright J, Tsakiridis T: Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways. Radiat Oncol 2011, 6:144. BioMed Central Full Text
• [18]Prescott E, Groenbaek M, Becker U, Soerensen T: Alcohol intake and the risk of lung cancer: influence of type of alcoholic beverage. Am J Epidemiol 1999, 149(5):463-470.
• [19]Benedetti A, Parent M, Siemiatycki J: Consumption of alcoholic beverages and risk of lung cancer: results from two case–control studies in Montreal, Canada. Cancer Causes Control 2006, 17(4):469-480.
• [20]Maxwell S, Cruickshank A, Thorpe G: Red wine and antioxidant activity in serum. Lancet 1994, 344(8916):193-194.
• [21]Grønbaek M, Becker U, Johansen D, Gottschau A, Schnohr P, Hein HO, Jensen G, Sørensen TI: Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Ann Intern Med 2000, 133(6):411-419.
• [22]Hakimuddin F, Paliyath G, Meckling K: Treatment of mcf-7 breast cancer cells with a red grape wine polyphenol fraction results in disruption of calcium homeostasis and cell cycle arrest causing selective cytotoxicity. J Agric Food Chem 2006, 54(20):7912-7923.
• [23]Briviba K, Pan L, Rechkemmer G: Red wine polyphenols inhibit the growth of colon carcinoma cells and modulate the activation pattern of mitogen-activated protein kinases. J Nutr 2002, 132(9):2814-2818.
• [24]Lee KW, Kang NJ, Heo YS, Rogozin EA, Pugliese A, Hwang MK, Bowden GT, Bode AM, Lee HJ, Dong Z: Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine. Cancer Res 2008, 68(3):946-955.
• [25]Aggarwal B, Bhardwaj A, Aggarwal R, Seeram N, Shishodia S, Takada Y: Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 2004, 24(5):A 2783-A 2840.
• [26]Yang CS, Landau JM, Huang MT, Newmark HL: Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr 2001, 21:381-406.
• [27]Albert S, Serova M, Dreyer C, Sablin MP, Faivre S, Raymond E: New inhibitors of the mammalian target of rapamycin signaling pathway for cancer. Expert Opin Investig Drugs 2010, 19(8):919-930.
• [28]Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, Bost F: Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther 2010, 9(5):1092-1099.
• [29]Kueck A, Opipari AW Jr, Griffith KA, Tan L, Choi M, Huang J, Wahl H, Liu JR: Resveratrol inhibits glucose metabolism in human ovarian cancer cells. Gynecol Oncol 2007, 107(3):450-457.
• [30]Zhu Z, Jiang W, McGinley JN, Thompson HJ: 2-Deoxyglucose as an energy restriction mimetic agent: effects on mammary carcinogenesis and on mammary tumor cell growth in vitro. Cancer Res 2005, 65(15):7023-7030.
• [31]Hernandez LG, Forkert PG: Inhibition of vinyl carbamate-induced mutagenicity and clastogenicity by the garlic constituent diallyl sulfone in F1 (Big Blue x A/J) transgenic mice. Carcinogenesis 2007, 28(8):1824-1830. Epub 2007 Mar 6
• [32]Tsakiridis T, Cutz JC, Singh G, Hirte H, Okawara G, Corbett T, Sur R, Cai W, Whelan T, Wright JR: Association of phosphorylated epidermal growth factor receptor with survival in patients with locally advanced non-small cell lung cancer treated with radiotherapy. J Thorac Oncol 2008, 3(7):716-722.
• [33]Kurtze I, Sonnemann J, Beck JF: KRAS-mutated non-small cell lung cancer cells are responsive to either co-treatment with erlotinib or gefitinib and histone deacetylase inhibitors or single treatment with lapatinib. Oncol Rep 2011, 25(4):1021-1029.
• [34]Sparwel J, Vantler M, Caglayan E, Kappert K, Fries J, Dietrich H, Bohm M, Erdmann E, Rosenkranz S: Differential effects of red and white wines on inhibition of the platelet-derived growth factor receptor: impact of the mash fermentation. Cardiovasc Res 2009, 81(4):758-770.
• [35]Li Y, Liu J, Liu X, Xing K, Wang Y, Li F, Yao L: Resveratrol-induced cell inhibition of growth and apoptosis in MCF7 human breast cancer cells are associated with modulation of phosphorylated Akt and caspase-9. Appl Biochem Biotechnol 2006, 135(3):181-192.
• [36]Sexton E, Van Themsche C, Leblanc K, Parent S, Lemoine P, Asselin E: Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells. Mol Cancer 2006, 5:45. BioMed Central Full Text
• [37]Shih A, Zhang S, Cao HJ, Boswell S, Wu YH, Tang HY, Lennartz MR, Davis FB, Davis PJ, Lin HY: Inhibitory effect of epidermal growth factor on resveratrol-induced apoptosis in prostate cancer cells is mediated by protein kinase C-alpha. Mol Cancer Ther 2004, 3(11):1355-1364.
• [38]Kim YA, Choi BT, Lee YT, Park DI, Rhee SH, Park KY, Choi YH: Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells. Oncol Rep 2004, 11(2):441-446.
• [39]Alkhalaf M: Resveratrol-induced apoptosis is associated with activation of p53 and inhibition of protein translation in T47D human breast cancer cells. Pharmacology 2007, 80(2–3):134-143.
• [40]Murias M, Luczak MW, Niepsuj A, Krajka-Kuzniak V, Zielinska-Przyjemska M, Jagodzinski PP, Jager W, Szekeres T, Jodynis-Liebert J: Cytotoxic activity of 3,3′,4,4′,5,5′-hexahydroxystilbene against breast cancer cells is mediated by induction of p53 and downregulation of mitochondrial superoxide dismutase. Toxicol In Vitro 2008, 22(5):1361-1370.
• [41]Zhang S, Cao HJ, Davis FB, Tang HY, Davis PJ, Lin HY: Oestrogen inhibits resveratrol-induced post-translational modification of p53 and apoptosis in breast cancer cells. Br J Cancer 2004, 91(1):178-185.
• [42]Vanamala J, Reddivari L, Radhakrishnan S, Tarver C: Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. BMC Cancer 2010, 10:238. BioMed Central Full Text
• [43]Narayanan BA, Narayanan NK, Re GG, Nixon DW: Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets. Int J Cancer 2003, 104(2):204-212.
• [44]Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellon EA: Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl 2007, 28(2):282-293.
• [45]Whyte L, Huang YY, Torres K, Mehta RG: Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res 2007, 67(24):12007-12017.
• [46]Walter A, Etienne-Selloum N, Brasse D, Khallouf H, Bronner C, Rio MC, Beretz A, Schini-Kerth VB: Intake of grape-derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis. FASEB J 2010, 24(9):3360-3369.
• [47]Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD: Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci U S A 1999, 96(24):13777-13782.
• [48]Carmi C, Mor M, Petronini PG, Alfieri R: Clinical perspectives for irreversible tyrosine kinase inhibitors in cancer. Biochem Pharmacol 2012, 84(11):1388-1399.
• [49]Ono M, Hirata A, Kometani T, Miyagawa M, Ueda S, Kinoshita H, Fujii T, Kuwano M: Sensitivity to gefitinib (Iressa, ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the epidermal growth factor (EGF) receptor/extracellular signal-regulated kinase 1/2 and EGF receptor/Akt pathway for proliferation. Mol Cancer Ther 2004, 3(4):465-472.
• [50]Nurgel C, Pickering GJ, Inglis D: Sensory and chemical characteristics of Canadian ice wines. J Sci Food Agric 2004, 84:1675-1684.
• [51]Iland P, Brauer N, Edwards G, Weeks S, Wilks E: Chemical Analysis of Grapes and Wines. Campbelltown, Australia: Wine Promotions Pty Ltd; 2004.
• [52]Breen DM, Sanli T, Giacca A, Tsiani E: Stimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK. Biochem Biophys Res Commun 2008, 374(1):117-122.
• [53]Zygmunt K, Faubert B, MacNeil J, Tsiani E: Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK. Biochem Biophys Res Commun 2010, 398(2):178-183.