Browse > Article
http://dx.doi.org/10.4174/jkss.2011.81.2.85

Induction of apoptosis with diallyl disulfide in AGS gastric cancer cell line  

Lee, Jeong-Eun (Department of Surgery, Hansol Hospital)
Lee, Ryung-Ah (Department of Surgery, Ewha Womans University School of Medicine)
Kim, Kwang-Ho (Department of Surgery, Ewha Womans University School of Medicine)
Lee, Joo-Ho (Department of Surgery, Ewha Womans University School of Medicine)
Publication Information
Annals of Surgical Treatment and Research / v.81, no.2, 2011 , pp. 85-95 More about this Journal
Abstract
Purpose: Diallyl disulfide (DADS) is a major organosulfur compound derived from garlic. It has been reported that DADS is able to inhibit the proliferation of several tumor cells. In this study, the effect of DADS was investigated in terms of the proliferation of AGS, gastric adenocarcinoma cell line at various concentrations. Methods: The viability of cultured cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To detect the induction of apoptosis, Annexin V-FITC/propodium iodide (PI) staining assay was performed. Analysis of reactive oxygen species (ROS) and the distribution of cells in the cell cycle were measured by a flow cytometer. And using the Western blot analysis, the change of Fas, caspase-3, Bax, Bcl-2 activity was measured. Results: The percentage of live AGS cells was decreased to 23% of that in the control group after 400 ${\mu}M$ DADS treatment for 48 hours. The Annexin V positive/PI negative (apoptosis portion) area increased from low concentration of DADS to high concentration. When comparing among the DADS treatment groups, the amount of ROS production increased in a dose dependent manner. The percentage of sub-diploid DNA content increased from 8.71% at 50 ${\mu}M$ to 25.74% at 400 ${\mu}M$ DADS treatment group. The expressions of Fas, caspase-3, Bax were increased and that of Bcl-2 was decreased in a dose dependent manner. Conclusion: DADS decreases the viability of AGS cell lines and induces apoptosis in a dose-dependent manner. But the relationship of the anti-proliferative effect of DADS and related molecular changes were not clearly proportional to the concentration of DADS.
Keywords
Diallyl disulfide; Gastric cancer cell line; Apoptosis;
Citations & Related Records

Times Cited By Web Of Science : 3  (Related Records In Web of Science)
Times Cited By SCOPUS : 4
연도 인용수 순위
  • Reference
1 Sun SY, Hail N Jr, Lotan R. Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 2004;96:662-72.
2 Fleischauer AT, Arab L. Garlic and cancer: a critical review of the epidemiologic literature. J Nutr 2001;131(3S):1032S- 40S.
3 Wargovich MJ, Uda N, Woods C, Velasco M, McKee K. Allium vegetables: their role in the prevention of cancer. Biochem Soc Trans 1996;24:811-4.
4 Milner JA. A historical perspective on garlic and cancer. J Nutr 2001;131(3S):1027S-31S.
5 Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a review. Crit Rev Food Sci Nutr 2004;44:479-88.
6 Lawson LD, Wang ZJ. Pre-hepatic fate of the organosulfur compounds derived from garlic (Allium sativum). Planta Med 1993;59:A688-9.
7 Bose C, Guo J, Zimniak L, Srivastava SK, Singh SP, Zimniak P, et al. Critical role of allyl groups and disulfide chain in induction of Pi class glutathione transferase in mouse tissues in vivo by diallyl disulfide, a naturally occurring chemopreventive agent in garlic. Carcinogenesis 2002;23:1661-5.   DOI   ScienceOn
8 Filomeni G, Aquilano K, Rotilio G, Ciriolo MR. Reactive oxygen species-dependent c-Jun NH2-terminal kinase/ c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide. Cancer Res 2003;63:5940-9.
9 Wu XJ, Kassie F, Mersch-Sundermann V. The role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human A549 lung carcinoma cells. Mutat Res 2005;579: 115-24.   DOI   ScienceOn
10 Kwon KB, Yoo SJ, Ryu DG, Yang JY, Rho HW, Kim JS, et al. Induction of apoptosis by diallyl disulfide through activation of caspase-3 in human leukemia HL-60 cells. Biochem Pharmacol 2002;63:41-7.
11 Nakagawa H, Tsuta K, Kiuchi K, Senzaki H, Tanaka K, Hioki K, et al. Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines. Carcinogenesis 2001;22: 891-7.   DOI   ScienceOn
12 Hong YS, Ham YA, Choi JH, Kim J. Effects of allyl sulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non small cell lung cancer cell lines. Exp Mol Med 2000;32:127-34.
13 Abraham KO, Shankaranarayana ML, Raghavan B, Nataraja CP. Alliums-varieties, chemistry, and analysis. Lebenson-Wiss U Technol 1976;9:193-200.
14 You WC, Blot WJ, Chang YS, Ershow A, Yang ZT, An Q, et al. Allium vegetables and reduced risk of stomach cancer. J Natl Cancer Inst 1989;81:162-4.   DOI
15 Song JD, Lee SK, Kim KM, Park SE, Park SJ, Kim KH, et al. Molecular mechanism of diallyl disulfide in cell cycle arrest and apoptosis in HCT-116 colon cancer cells. J Biochem Mol Toxicol 2009;23:71-9.
16 Wan X, Polyakova Y, Row KH. Determination of diallyl disulfide in garlic by reversed-phase high performance liquid chromatography. Anal Sci Technol 2007;20:442-7.
17 Hong WK, Sporn MB. Recent advances in chemoprevention of cancer. Science 1997;278:1073-7.   DOI   ScienceOn
18 Omkumar RV, Kadam SM, Banerji A, Ramasarma T. On the involvement of intramolecular protein disulfide in the irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by diallyl disulfide. Biochim Biophys Acta 1993;1164:108-12.
19 Hengartner MO. The biochemistry of apoptosis. Nature 2000;407:770-6.   DOI   ScienceOn
20 Oez S, Platzer E, Welte K. A quantitative colorimetric method to evaluate the functional state of human polymorphonuclear leukocytes. Blut 1990;60:97-102.
21 Wang X, Martindale JL, Liu Y, Holbrook NJ. The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem J 1998;333(Pt 2):291-300.
22 Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell 1997;88:347-54.
23 Carmody RJ, Cotter TG. Signalling apoptosis: a radical approach. Redox Rep 2001;6:77-90.
24 Peter ME, Krammer PH. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 2003;10:26-35.
25 Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997;90:405-13.
26 Ruvolo PP, Deng X, May WS. Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia 2001;15:515-22.
27 Filomeni G, Aquilano K, Rotilio G, Ciriolo MR. Glutathione- related systems and modulation of extracellular signal- regulated kinases are involved in the resistance of AGS adenocarcinoma gastric cells to diallyl disulfide-induced apoptosis. Cancer Res 2005;65:11735-42.
28 Herman-Antosiewicz A, Powolny AA, Singh SV. Molecular targets of cancer chemoprevention by garlic-derived organosulfides. Acta Pharmacol Sin 2007;28:1355-64.
29 Yuan JP, Wang GH, Ling H, Su Q, Yang YH, Song Y, et al. Diallyl disulfide-induced G2/M arrest of human gastric cancer MGC803 cells involves activation of p38 MAP kinase pathways. World J Gastroenterol 2004;10:2731-4.