Resveratrol-fortification of red wine does not provide greater inhibition of human lung cancer cell survival compared to non-fortified wine.

Jessy Moore; Gary Pickering; Nicole J Gaudette; Evangelia Tsiani

Resveratrol-fortification of red wine does not provide greater inhibition of human lung cancer cell survival compared to non-fortified wine.

Jessy Moore, Gary Pickering, Nicole J Gaudette, Evangelia Tsiani

Abstract

Lung cancer is the leading cause of cancer-related deaths, and individuals with this disease often develop resistance to conventional cytotoxic therapies. Red wine and its polyphenolic component resveratrol, have been shown to have anticancer effects. Wines fortified with resveratrol have been marketed as having additional health benefits because of their increased polyphenolic content, however no studies exist examining this claim. The aim of the present study was to explore the effects of resveratrol-fortified red wine on lung cancer cell survival. Human NSCLC A549 cells were treated with varying concentrations of red wine with or without trans-resveratrol fortification. Cell survival was assessed using clonogenic assays and immunoblotting was used to explore the effects on Akt and ERK signaling molecules. Red wine significantly inhibited cell survival at concentrations as low as 0.02%, and significantly reduced phosphorylation of both Akt and ERK. No significant differences were seen between regular and resveratrol-fortified red wine. These data suggest that red wine may have considerable cancer preventive potential, however it does not support the use of resveratrol-fortified wine for additional health benefits.

Keywords

cancer, survival, Akt, ERK, red wine, resveratrol

References

Aluyen JK, Ton QN, Tran T, Yang AE, Gottlieb HB & Bellanger RA 2012 Resveratrol: Potential as Anticancer Agent. J Diet Suppl 9 45-56

Barron CC, Moore J, Tsakiridis T, Pickering G & Tsiani E 2014 Inhibition of human lung cancer cell proliferation and survival by wine. Cancer Cell Int 14 6

Bishayee A & Dhir N 2009 Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: Inhibition of cell proliferation and induction of apoptosis. Chem Biol Interact 179 131-144

Brognard J, Clark AS, Ni Y & Dennis PA 2001 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 61 3986-3997

Castillo-Pichardo L, Martínez-Montemayor MM, Martínez JE, Wall KM, Cubano LA & Dharmawardhane S 2009 Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols. Clin Exp Metastasis 26 505-516

Ciuffreda L, Incani UC, Steelman LS, Abrams SL, Falcone I, Curatolo AD, Chappell WH, Franklin RA, Vari S, Cognetti F, McCubrey JA & Milella M 2014 Signaling intermediates (MAPK and PI3K) as therapeutic targets in NSCLC. Curr Pharm Des 20 3944-3957

Elattar T & Virji A 1998 The effect of red wine and its components on growth and proliferation of human oral squamous carcinoma cells. Anticancer Res 19 5407-5414

Ermoian RP, Furniss CS, Lamborn KR, Basila D, Berger MS, Gottschalk AR, Nicholas MK, Stokoe D & Haas-Kogan DA 2002 Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin Cancer Res 8 1100-1106

Gaudette NJ & Pickering GJ 2011 Sensory and chemical characteristics of trans-resveratrol-fortified wine. Australian J Grape Wine Res 17 249-257

Gaudette NJ & Pickering GJ 2013 Modifying Bitterness in Functional Food Systems. Crit Rev Food Sci Nutr 53 464-481

Gentry L, Samatar AA & Der CJ 2013 Inhibitors of the ERK mitogen-activated protein kinase cascade for targeting RAS mutant cancers. The Enzymes 34 67-106

German JB & Walzem RL 2000 The Health Benefits of Wine. Ann Rev Nutr 20 561-593

Golkar L, Ding XZ, Ujiki MB, Salabat MR, Kelly DL, Scholtens D, Fought AJ, Bentrem DJ, Talamonti MS, Bell RH & Adrian TE 2007 Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1. J Surg Res 138 163-169

Granado-Serrano AB, Martín MA, Bravo L, Goya L & Ramos S 2006 Quercetin Induces Apoptosis via Caspase Activation, Regulation of Bcl-2, and Inhibition of PI-3-Kinase/Akt and ERK Pathways in a Human Hepatoma Cell Line (HepG2). J Nutr 136 2715-2721

Hanahan D & Weinberg RA 2011 Hallmarks of Cancer: The Next Generation. Cell 144 646-674

Harper CE, Patel BB, Wang J, Arabshahi A, Eltoum IA & Lamartiniere CA 2007 Resveratrol suppresses prostate cancer progression in transgenic mice. Carcinogenesis 28 1946-1953

Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC & Pezzuto JM 1997 Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275 218-220

Jones GC, Kehrer JD, Kahn J, Koneru BN, Narayan R, Thomas TO, Camphausen K, Mehta MP & Kaushal A 2015 Primary Treatment Options for High-Risk/Medically Inoperable Early Stage NSCLC Patients. Clin Lung Cancer 16 413-430

Kampa M, Hatzoglou A, Notas G, Damianaki A, Bakogeorgou E, Gemetzi C, Kouroumalis E, Martin PM & Castanas E 2003 Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines. Nutr Cancer 37 223-233

Kubota T, Uemura Y, Kobayashi M & Taguchi H 2002 Combined effects of resveratrol and paclitaxel on lung cancer cells. Anticancer Res 23 4039-4046

Liu LZ, Zhou XD, Qian G, Shi X, Fang J & Jiang BH 2007 AKT1 Amplification Regulates Cisplatin Resistance in Human Lung Cancer Cells through the Mammalian Target of Rapamycin/p70S6K1 Pathway. Cancer Res 67 6325-6332

Liu P, Cheng H, Roberts TM & Zhao JJ 2009 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Dis 8 627-644

Manning BD & Cantley LC 2007 AKT/PKB Signaling: Navigating Downstream. Cell, 129(7), 1261-1274

Martínez C, Vicente V, Yáñez J, Alcaraz M, Castells MT, Canteras M, Benavente-García O & Castillo J 2005 The effect of the flavonoid diosmin, grape seed extract and red wine on the pulmonary metastatic B16F10 melanoma. Histol Histopathol 20 1121-1129

Mattivi F, Reniero F & Korhammer S 1995 Isolation, Characterization, and Evolution in Red Wine Vinification of Resveratrol Monomers. J Agricult Food Chem 43 1820-1823

Mayo LD & Donner DB 2001 A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci U S A 98 11598-11603

Norrie P 2009 Guest Editorial: Resveratrol-enhanced wine. Int J Wine Res 2009 187-188

Pérez-Tenorio G & Stål O 2002 Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Brit J Cancer 86 540-545

Rashid A, Liu C, Sanli T, Tsiani E, Singh G, Bristow RG, Dayes I, Lukka H, Wright J & Tsakiridis T 2011 Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways. Radiat Oncol 6 144

Roberts PJ & Der CJ 2007 Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26 3291-3310

Rothschild SI 2015 Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK. Cancers 7 930-949

Schlachterman A, Valle F, Wall KM, Azios NG, Castillo L, Morell L, Washington AV, Cubano LA & Dharmawardhane SF 2008 Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl Oncol 1 19-27

Sexton É, Themsche CV, Leblanc K, Parent S, Lemoine P & Asselin E 2006 Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells. Mol Cancer 5 45

Smoliga JM & Blanchard O 2014 Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution? Molecules (Basel, Switzerland) 19 17154-17172

Stewart BW & Wild CP 2014 World cancer report 2014 World Health Organization.

Sun C, Hu Y, Liu X, Wu T, Wang Y, He W & Wei W 2006 Resveratrol downregulates the constitutional activation of nuclear factor-κB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis. Cancer Gen Cytogen 165 9-19

Tessitore L, Davit A, Sarotto I & Caderni G 2000 Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21CIP expression. Carcinogenesis 21 1619-1622

Thomas A, Liu SV, Subramaniam DS & Giaccone G 2015 Refining the treatment of NSCLC according to histological and molecular subtypes. Nat Rev Clin Oncol 12 511-526

Wallenborg K, Vlachos P, Eriksson S, Huijbregts L, Arnér ES, Joseph B & Hermanson O 2009 Red wine triggers cell death and thioredoxin reductase inhibition: Effects beyond resveratrol and SIRT1. Experimental Cell Research 315 1360-1371

Walter A, Etienne-Selloum N, Brasse D, Khallouf H, Bronner C, Rio MC, Beretz A & Schini-Kerth VB. 2010 Intake of grape-derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis. FASEB J 24 3360-3369

Yang X, Li X & Ren J 2014 From French Paradox to cancer treatment: anti-cancer activities and mechanisms of resveratrol. AntiCancer Agents Med Chem 14 806-825

Zordoky BN, Robertson IM & Dyck JR 2015 Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochim Biophys Acta 1852 1155-1177

Full Text: PDF

Refbacks

There are currently no refbacks.