Induction of Quinone Reductase and Glutathion S-transferase in Hepatoma Cells by Citrus aurantium Linn (Jikak) Produced in Cheju Island

지각 추출물이 quinone reductase 및 glutathion s-transferase의 유도활성에 미치는 영향

  • Yu, Mi-Hee (Department of Food Science and Technology, School of Natural Science, Keimyung University) ;
  • Lee, In-Seon (The Center for Traditional Microorganism Resources, Keimyung University)
  • 유미희 (계명대학교 식품가공학 전공) ;
  • 이인선 (계명대학교 전통미생물자원개발 및 산업화연구(TMR) 센터)
  • Published : 2005.04.30


Phase II enzymes are transcriptionally induced by synthetic chemical agents and natural products, and such induction plays critical roles in protection against chemical carcinogens and other toxic xenobiotics. To discover natural products for use as cancer chemopreventive agents, the ability of Citrus aurantium Linn (Jikak) to induce activities of quinone reductase (QR) and glutathione S-transferase (GST) in wild-type murine hepatoma cell line (Hepa 1c1c7) and Ah-receptor-defective mutant of the same cell line (Bprcl) was investigated. Hexane and chloroform fractions of C. aurantium Linn (Jikak) at doses not exhibiting cytotoxicity were effective inducers of QR (${\sim}1.8-fold$) and GST (${\sim}1.5-fold$) in Hepa 1c1c7 cells, whereas showed low QR induction potency in Bprcl cells, which indicates they have weak monofunctional action. Results suggest C. aurantium Linn (Jikak) as potentially useful cancer chemopteventive agent.


  1. Kang GI. The conception by drugs of medical action and activity. pp. 245, 286-302. Hiseongchulpansa, Seoul, Korea (1993)
  2. Prochaska HJ, Talalay P. Regulatory mechanisms of monofunctional and bifunctional anticarcinogenic enzyme inducers in murine liver. Cancer Res. 48: 4776-4782 (1988)
  3. Kwak YJ, Jun HJ, Kwon TW, Kim JS. Modulation of anticarcinogenic enzyme and plasma testosterone level in male mouse fed leek-supplemented diet. Korean J. Food Sci. Nutr. 27: 968-972 (1998)
  4. Kim SM, Ryu SH, Choi RD, Kim SS, Kim JH, Kim JS. Screening for Korean vegetables with anticarcinogenic enzyme inducing activity using cell culture system. Korean J. Food Sci. Nutr. 27: 277-28l (1998)
  5. Hwang HJ, Yoon KR. Carotenoid pigment of citrus fruits cultivated in Korea. Food Biotechnol. 27: 950-957 (1995)
  6. Eun JB, Jung YM, Woo GJ. Identification and determination of dietary fibers and flavonoids and peel of Korean Tangerine (Citrus aurantium var.). Korean J. Food Sci. Technol. 28: 371-377 (1996)
  7. Oh HS, Park WB, An YS, Oh MC, Oh CK, Kim SH. Antimicrobial activity of extracts from citrus seeds. Korean J. Culinary Res. 9: 69-80 (2003)
  8. Green LM, Reade JL, Ware CF. Rapid colormetric assay for cell viability: Application to the quantitation of cytotoxic and growth inhibitory lympokines. J. Immunol. Method 70: 257-268 (1984)
  9. Benson A, Hunkeler MJ, Talay P. Increase of NAD(P)H: qunone reductase by dietary antioxidants. Possible role in protection against carcinogenesis and toxicity. Proc. Natl. Acad. Sci. USA 77: 5216-5220 (1980)
  10. Kim JS, Nam YJ, Kwon TW. Induction of quinone reductase activity by genistein, soybean isoflavone. Food Sci. Biotech. 5: 70-75 (1996)
  11. Williamson G, DuPont MS, Wanigatunga S, Heaney RK, Musk SRR, Fenwick GR, Hodes MJC. Induction of glutathione S-transferase activity in hepG2 cells by extracts from fruits and vegetables. Food Chem. 60: 157-160 (1997)
  12. Talalay P, Benson AM. Elvation of quinone reductase activity by anticarcinogenic antioxidants. Adv. Enzyme Reg. 20: 287-300 (1982)
  13. Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: Islation and elucidation of structure. Proc. Natl. Acad. Sci. USA 89: 2399-2403 (1992)
  14. Mehta RG, Liu J, Constantinou A, Thomas CF, Hawthorne M, Gerhuser C, Pezzuto, JM, Moon RC, Moriarty RM. Cancer chemopreventive activity of brassinin, a phytoalexin from cabbage. Carcinogenesis 16: 399-404 (1995)
  15. Kim HS, Kacew S, Lee BM. In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis Miller, Lentinus edodes, Ganoderma lucidum and Corious versicolor). Carcinogenesis 20: 1637-1640 (1999)
  16. Wefers H, Komai T, Talalay P, Sies H. Protection against reactive oxygen species by NAD(P)H: quinone recuctase induced by the dietary antioxidant butylated hydroxyanisole (BHA). FEBS Lett. 169: 63-66 (1984)
  17. Habig WH, Pabist MJ, Iakoby WB. Glutathione S-transferase: The first enzymetic step in merapturic acid formation. J. BioI. Chem. 25: 7130-7139 (1974)
  18. Talalay P, De Long MJ, Prochaska HJ. Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis. Proc. Natl. Acad. Sci. USA 85: 8261-8265 (1988)
  19. Gerhauser C, You M, Liu J, Moriarty RM, Hawthorne M, Mehta RG, Moon RC, Pezzuto JM. Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes. Cancer Res. 57: 272-278 (1997)
  20. Drysdale BE, Zacharchuk CM, Okajima M, Shin HS. In Methods in Enaymology (Di Sabato G, and Eberse T., Eds.). Academic press: Orlando. FL. 132: 549-555 (1986)
  21. Spencer SR, Wilczak CA, Talalay P. Induction of glutathione transferases and NAD(P)H: Quinone reductase by fumaric acid derivatives in rodent cells and tissues. Cancer Res. 50: 7871-7875 (1990)
  22. Oshiba J, Kato M. Nutritional regulation III, depression of cardiac action by the isolated naringin, Mukogawa Joshidaigaku Kiyo. 29: 1-8 (1981)
  23. Hashimoto K, Kawamata S, Usui N, Tanaka A, Uda Y. In vitro induction of the anticarcinogenic marker enzyme, quinone reductase, in human hepatoma cells by food extracts. Cancer Lett. 180: 1-5 (2002)
  24. Koh JS, Kim SH. Physicochemical properties and chemical compositions of citrus fruits produced in Cheju, Agric. Chem. Biotechnol. 38: 541-545 (1995)
  25. Prochaska HJ, Santamaria AB. Direct measurement of NAD(P)H: Quinone reductase from cells cultured in microtiter well: A screening assay for anticarcinogenic enzyme inducers. Anal. Biochem. 169: 328-336 (1988)