Cyanidin-3-Glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2

Molecular Cancer - Tập 9 - Trang 1-14 - 2010
Mei Xu1, Kimberly A Bower1, Siying Wang1,2, Jacqueline A Frank1, Gang Chen1, Min Ding3, Shiow Wang4, Xianglin Shi5, Zunji Ke6, Jia Luo1
1Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, USA
2Pathophysiological Department, School of Basic Medicine, Anhui Medical University, Hefei, China
3National Institute for Occupational Safety and Health, Morgantown, USA
4Beltsville Agricultural Research Center, U. S. Department of Agriculture, Beltsville, USA
5Graduate Center for Toxicology, University of Kentucky, Lexington, USA
6Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

Tóm tắt

Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7ErbB2) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130Cas/JNK interaction. C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

Tài liệu tham khảo

Key J, Hodgson S, Omar RZ, Jensen TK, Thompson SG, Boobis AR, Davies DS, Elliott P: Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes Control. 2006, 17: 759-70. 10.1007/s10552-006-0011-0 Seitz HK, Maurer B: The relationship between alcohol metabolism, estrogen levels, and breast cancer risk. Alcohol Res Health. 2007, 30: 42-3. Seitz HK, Becker P: Alcohol metabolism and cancer risk. Alcohol Res Health. 2007, 30: 38-7. Tjonneland A, Christensen J, Olsen A, Stripp C, Thomsen BL, Overvad K, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Ocke MC, Thiebaut A, Fournier A, Clavel-Chapelon F, Berrino F, Palli D, Tumino R, Panico S, Vineis P, Agudo A, Ardanaz E, Martinez-Garcia C, Amiano P, Navarro C, Quiros JR, Key TJ, Reeves G, Khaw KT, Bingham S, Trichopoulou A, Trichopoulos D, Naska A, Nagel G, Chang-Claude J, Boeing H, Lahmann PH, Manjer J, Wirfalt E, Hallmans G, Johansson I, Lund E, Skeie G, Hjartaker A, Ferrari P, Slimani N, Kaaks R, Riboli E: Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2007, 18: 361-73. 10.1007/s10552-006-0112-9 Visvanathan K, Crum RM, Strickland PT, You X, Ruczinski I, Berndt SI, Alberg AJ, Hoffman SC, Comstock GW, Bell DA, Helzlsouer KJ: Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer. Alcohol Clin Exp Res. 2007, 31: 467-76. 10.1111/j.1530-0277.2006.00334.x Vaeth PA, Satariano WA: Alcohol consumption and breast cancer stage at diagnosis. Alcohol Clin Exp Res. 1998, 22: 928-34. Weiss HA, Brinton LA, Brogan D, Coates RJ, Gammon MD, Malone KE, Schoenberg JB, Swanson CA: Epidemiology of in situ and invasive breast cancer in women aged under 45. Br J Cancer. 1996, 73: 1298-305. Aye MM, Ma C, Lin H, Bower KA, Wiggins RC, Luo J: Ethanol-induced in vitro invasion of breast cancer cells: the contribution of MMP-2 by fibroblasts. Int J Cancer. 2004, 112: 738-46. 10.1002/ijc.20497 Ke Z, Lin H, Fan Z, Cai TQ, Kaplan RA, Ma C, Bower KA, Shi X, Luo J: MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2. Int J Cancer. 2006, 119: 8-16. 10.1002/ijc.21769 Ma C, Lin H, Leonard SS, Shi X, Ye J, Luo J: Overexpression of ErbB2 enhances ethanol-stimulated intracellular signaling and invasion of human mammary epithelial and breast cancer cells in vitro. Oncogene. 2003, 22: 5281-90. 10.1038/sj.onc.1206675 Paterson MC, Dietrich KD, Danyluk J, Paterson AH, Lees AW, Jamil N, Hanson J, Jenkins H, Krause BE, McBlain WA: Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. Cancer Res. 1991, 51: 556-67. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987, 235: 177-82. 10.1126/science.3798106 Chen PN, Chu SC, Chiou HL, Chiang CL, Yang SF, Hsieh YS: Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo. Nutr Cancer. 2005, 53: 232-43. 10.1207/s15327914nc5302_12 Ding M, Feng R, Wang SY, Bowman L, Lu Y, Qian Y, Castranova V, Jiang BH, Shi X: Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J Biol Chem. 2006, 281: 17359-68. 10.1074/jbc.M600861200 Shih PH, Yeh CT, Yen GC: Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells. Food Chem Toxicol. 2005, 43: 1557-66. 10.1016/j.fct.2005.05.001 Zhang Y, Vareed SK, Nair MG: Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sci. 2005, 76: 1465-72. 10.1016/j.lfs.2004.08.025 Fukamachi K, Imada T, Ohshima Y, Xu J, Tsuda H: Purple corn color suppresses Ras protein level and inhibits 7, 12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in the rat. Cancer Sci. 2008, 99: 1841-6. 10.1111/j.1349-7006.2008.00732.x Zhang Y, Seeram NP, Lee R, Feng L, Heber D: Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties. J Agric Food Chem. 2008, 56: 670-5. 10.1021/jf071989c Xu M, Bower KA, Chen G, Shi X, Dong Z, Ke Z, Luo J: Ethanol enhances the interaction of breast cancer cells over-expressing ErbB2 with fibronectin. Alcohol Clin Exp Res. 2010, 34: 751-60. 10.1111/j.1530-0277.2010.01147.x Grimaldi C, Pisanti S, Laezza C, Malfitano AM, Santoro A, Vitale M, Caruso MG, Notarnicola M, Iacuzzo I, Portella G, Di M, Bifulco M: Anandamide inhibits adhesion and migration of breast cancer cells. Exp Cell Res. 2006, 312: 363-73. 10.1016/j.yexcr.2005.10.024 Wang F, Nohara K, Olivera A, Thompson EW, Spiegel S: Involvement of focal adhesion kinase in inhibition of motility of human breast cancer cells by sphingosine 1-phosphate. Exp Cell Res. 1999, 247: 17-28. 10.1006/excr.1998.4327 Xu M, Waters CL, Hu C, Wysolmerski RB, Vincent PA, Minnear FL: Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase. Am J Physiol Cell Physiol. 2007, 293: C1309-C1318. 10.1152/ajpcell.00014.2007 Chen G, Bower KA, Xu M, Ding M, Shi X, Ke ZJ, Luo J: Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3 Beta. Neurotox Res. 2009, 15: 321-31. 10.1007/s12640-009-9036-y Vadlamudi RK, Sahin AA, Adam L, Wang RA, Kumar R: Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215. FEBS Lett. 2003, 543: 76-80. 10.1016/S0014-5793(03)00404-6 Dolfi F, Garcia-Guzman M, Ojaniemi M, Nakamura H, Matsuda M, Vuori K: The adaptor protein Crk connects multiple cellular stimuli to the JNK signaling pathway. Proc Natl Acad Sci USA. 1998, 95: 15394-9. 10.1073/pnas.95.26.15394 Klemke RL, Leng J, Molander R, Brooks PC, Vuori K: Cheresh DA, CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. J Cell Biol. 1998, 140: 961-72. 10.1083/jcb.140.4.961 Cox BD, Natarajan M, Stettner MR, Gladson CL: New concepts regarding focal adhesion kinase promotion of cell migration and proliferation. J Cell Biochem. 2006, 99: 35-52. 10.1002/jcb.20956 Huang C, Jacobson K, Schaller MD: MAP kinases and cell migration. J Cell Sci. 2004, 117: 4619-28. 10.1242/jcs.01481 Yamaguchi H, Wyckoff J, Condeelis J: Cell migration in tumors. Curr Opin Cell Biol. 2005, 17: 559-64. 10.1016/j.ceb.2005.08.002 Turner CE: Paxillin interactions. J Cell Sci. 2000, 113 (Pt 23): 4139-40. Chen G, Ma C, Bower KA, Shi X, Ke Z, Luo J: Ethanol promotes endoplasmic reticulum stress-induced neuronal death: involvement of oxidative stress. J Neurosci Res. 2008, 86: 937-46. 10.1002/jnr.21540 Zheng W, Wang SY: Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries. J Agric Food Chem. 2003, 51: 502-9. 10.1021/jf020728u Chen G, Luo J: Anthocyanins: are they beneficial in treating ethanol neurotoxicity?. Neurotox Res. 2010, 17: 91-101. 10.1007/s12640-009-9083-4 Chen PN, Kuo WH, Chiang CL, Chiou HL, Hsieh YS, Chu SC: Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. Chem Biol Interact. 2006, 163: 218-29. 10.1016/j.cbi.2006.08.003 Hao H, Naomoto Y, Bao X, Watanabe N, Sakurama K, Noma K, Motoki T, Tomono Y, Fukazawa T, Shirakawa Y, Yamatsuji T, Matsuoka J, Wang ZG, Takaoka M: Focal adhesion kinase as potential target for cancer therapy (Review). Oncol Rep. 2009, 22: 973-9. 10.3892/or_00000573 Schwock J, Dhani N, Hedley DW: Targeting focal adhesion kinase signaling in tumor growth and metastasis. Expert Opin Ther Targets. 2010, 14: 77-94. 10.1517/14728220903460340 Benlimame N, He Q, Jie S, Xiao D, Xu YJ, Loignon M, Schlaepfer DD, Alaoui-Jamali MA: FAK signaling is critical for ErbB-2/ErbB-3 receptor cooperation for oncogenic transformation and invasion. J Cell Biol. 2005, 171: 505-16. 10.1083/jcb.200504124 Earley S, Plopper GE: Phosphorylation of focal adhesion kinase promotes extravasation of breast cancer cells. Biochem Biophys Res Commun. 2008, 366: 476-82. 10.1016/j.bbrc.2007.11.181 Vadlamudi RK, Sahin AA, Adam L, Wang RA, Kumar R: Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215. FEBS Lett. 2003, 543: 76-80. 10.1016/S0014-5793(03)00404-6 Vadlamudi RK, Adam L, Nguyen D, Santos M, Kumar R: Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2. J Cell Physiol. 2002, 190: 189-99. 10.1002/jcp.10054 Xu M, Bower KA, Chen G, Shi X, Dong Z, Ke Z, Luo J: Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 With Fibronectin. Alcohol Clin Exp Res. 2010, 34 (5): 751-60. 10.1111/j.1530-0277.2010.01147.x Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA: CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. J Cell Biol. 1998, 140: 961-72. 10.1083/jcb.140.4.961 Takino T, Nakada M, Miyamori H, Watanabe Y, Sato T, Gantulga D, Yoshioka K, Yamada KM, Sato H: JSAP1/JIP3 cooperates with focal adhesion kinase to regulate c-Jun N-terminal kinase and cell migration. J Biol Chem. 2005, 280: 37772-81. 10.1074/jbc.M505241200 von Montfort C, Fernau NS, Beier JI, Sies H, Klotz LO: Extracellular generation of hydrogen peroxide is responsible for activation of EGF receptor by ultraviolet A radiation. Free Radic Biol Med. 2006, 41: 1478-87. 10.1016/j.freeradbiomed.2006.08.005 Marczylo TH, Cooke D, Brown K, Steward WP, Gescher AJ: Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice. Cancer Chemother Pharmacol. 2009, 64: 1261-8. 10.1007/s00280-009-0996-7