Browse > Article
http://dx.doi.org/10.4014/jmb.1503.03059

Dealcoholized Korean Rice Wine (Makgeolli) Exerts Potent Anti-Tumor Effect in AGS Human Gastric Adenocarcinoma Cells and Tumor Xenograft Mice  

Shin, Eun Ju (Korea Food Research Institute)
Kim, Sung Hee (Korea Food Research Institute)
Kim, Jae Ho (Korea Food Research Institute)
Ha, Jaeho (Korea Food Research Institute)
Hwang, Jin-Taek (Korea Food Research Institute)
Publication Information
Journal of Microbiology and Biotechnology / v.25, no.9, 2015 , pp. 1485-1492 More about this Journal
Abstract
Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.
Keywords
Makgeolli; anti-cancer; anti-angiogenesis; AGS human gastric adenocarcinoma cells; tumor xenograft;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Stärkel P, Charette N, Borbath I, Schneider-Merck T, De Saeger C, Abarca J, et al. 2012. Ras inhibition in hepatocarcinoma by S-trans-trans-farnesylthiosalicyclic acid: association of its tumor preventive effect with cell proliferation, cell cycle events, and angiogenesis. Mol. Carcinog. 51: 816-825.   DOI
2 Su CH, Chen LJ, Liao JF, Cheng JT. 2013. Increase of phosphatase and tensin homolog by silymarin to inhibit human pharynx squamous cancer. J. Med. Food 16: 778-784.   DOI
3 Sun CC, Zhang YS, Xue X, Cheng YN, Liu HP, Zhao CR, et al. 2011. Inhibition of angiogenesis involves in anticancer activity of riccardin D, a macrocyclic bisbibenzyl, in human lung carcinoma. Eur. J. Pharmacol. 667: 136-143.   DOI
4 Wu Y, Liu F. 2013. Targeting mTOR: evaluating the therapeutic potential of resveratrol for cancer treatment. Anticancer Agents Med. Chem. 13: 1032-1038.   DOI
5 Yang MH, Kim J, Khan IA, Walker LA, Khan SI. 2014. Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents. Life Sci. 100: 75-84.   DOI
6 Yun TK. 2003. Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutat. Res. 523: 63-74.   DOI
7 Zhang H, Xu HL, Fu WW, Xin Y, Li MW, Wang SJ, et al. 2014. 20(S)-Protopanaxadiol induces human breast cancer MCF-7 apoptosis through a caspase-mediated pathway. Asian Pac. J. Cancer Prev. 15: 7919-7923.   DOI
8 Zhao Z, Holle L, Song W, Wei Y, Wagner TE, Yu X. 2011. Antitumor and anti-angiogenic activities of Scutellaria barbata extracts in vitro are partially mediated by inhibition of Akt/protein kinase B. Mol. Med. Rep. 5: 788-792.
9 Lehman JA, Waning DL, Batuello CN, Cipriano R, Kadakia MP, Mayo LD. 2011. Induction of apoptotic genes by a p73-phosphatase and tensin homolog (p73-PTEN) protein complex in response to genotoxic stress. J. Biol. Chem. 286: 36631-36640.   DOI
10 Lee HJ, Lee EO, Rhee YH, Ahn KS, Li GX, Jiang C, et al. 2006. An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis. Carcinogenesis 27: 2455-2463.   DOI
11 Li Y, Kong D, Bao B, Ahmad A, Sarkar FH. 2011. Induction of cancer cell death by isoflavone: the role of multiple signaling pathways. Nutrients 3: 877-896.   DOI
12 Mukhtar E, Adhami VM, Khan N, Mukhtar H. 2012. Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents. Curr. Drug Targets 13: 1831-1841.   DOI
13 Pandurangan AK. 2013. Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac. J. Cancer Prev. 14: 2201-2205.   DOI
14 Park KY, Lee HJ, Jeong SJ, Lee HJ, Kim HS, Kim SH, et al. 2010. 1,2,3,4,6-Penta-O-galloly-beta-D-glucose suppresses hypoxiainduced accumulation of hypoxia-inducible factor-1α and signaling in LNCaP prostate cancer cells. Biol. Pharm. Bull. 33: 1835-1840.   DOI
15 Pinto MP, Dye WW, Jacobsen BM, Horwitz KB. 2014. Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling. BMC. Cancer 14: 735.   DOI
16 Shankar S, Srivastava RK. 2007. Involvement of Bcl-2 family members, phosphatidylinositol 3’-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int. J. Oncol. 30: 905-918.
17 Ha J, Wang Y, Jang H, Seog H, Chen X. 2014. Determination of E,E-farnesol in makgeolli (rice wine) using dynamic headspace sampling and stir bar sorptive extraction coupled with gas chromatography-mass spectrometry. Food Chem. 142: 79-86.   DOI
18 Joo JH, Jetten AM. 2010. Molecular mechanisms involved in farnesol-induced apoptosis. Cancer Lett. 287: 123-135.   DOI
19 Hassan B, Akcakanat A, Holder AM, Meric-Bernstam F. 2013. Targeting the PI3-kinase/Akt/mTOR signaling pathway. Surg. Oncol. Clin. N. Am. 22: 641-664.   DOI
20 Hu Y, Wang S, Wu X, Zhang J, Chen R, Chen M, Wang Y. 2013. Chinese herbal medicine-derived compounds for cancer therapy: a focus on hepatocellular carcinoma. J. Ethnopharmacol. 149: 601-612.   DOI
21 Jung H, Lee SJ, Lim JH, Kim BK, Park KJ. 2014. Chemical and sensory profiles of makgeolli, Korean commercial rice wine, from descriptive, chemical, and volatile compound analyses. Food Chem. 152: 624-632.   DOI
22 Kang BS, Lee JE, Park HJ. 2014. Qualitative and quantitative prediction of volatile compounds from initial amino acid profiles in Korean rice wine (makgeolli) model. J. Food Sci. 79: C1106-C1116.   DOI
23 Khuda-Bukhsh AR, Das S, Saha SK. 2014. Molecular approaches toward targeted cancer prevention with some food plants and their products: inflammatory and other signal pathways. Nutr. Cancer 66: 194-205.   DOI
24 Kitagishi Y, Matsuda S, Minami A, Ono Y, Nakanishi A, Ogura Y. 2014. Regulation in cell cycle via p53 and PTEN tumor suppressors Cancer Stud. Mol. Med. Open J. 1: 1-7.   DOI
25 Arumugam A, Agullo P, Boopalan T, Nandy S, Lopez R, Gutierrez C, et al. 2014. Neem leaf extract inhibits mammary carcinogenesis by altering cell proliferation, apoptosis, and angiogenesis. Cancer Biol. Ther. 15: 26-34.   DOI
26 Chen Q, Ganapathy S, Singh KP, Shankar S, Srivastava RK. 2010. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. PLoS One 5: e15288.   DOI
27 Crane C, Panner A, Pieper RO, Arbiser J, Parsa AT. 2009. Honokiol-mediated inhibition of PI3K/mTOR pathway: a potential strategy to overcome immunoresistance in glioma, breast, and prostate carcinoma without impacting T cell function. J. Immunother. 32: 585-592.   DOI