Anticancer Effect of Erythronium japonicum Extract on ICR Mouse and L1210 Cells with Alteration of Antioxidant Enzyme Activities

얼레지 추출물의 ICR 마우스와 L1210 암세포에 대한 항암작용과 그에 따른 항산화효소 활성변화

  • Shin, Yoo-Jin (Department of Chemistry, Sangmyung University) ;
  • Jung, Dae-Young (Department of Herbal Pharmaceutical Medicine, Korea Institute of Oriental Medicine) ;
  • Ha, Hye-Kyung (Department of Chemistry, Sangmyung University) ;
  • Park, Sie-Won (Department of Chemistry, Sangmyung University)
  • Published : 2004.12.31


Effects of Erythronium japonicum methanol extract on ICR mouse with induced abdominal cancer and L1210 cells were studied. Administration of methanol extract ($10-100\;{\mu}g/20\;g$ body weight) prolonged life by 47.8% and decreased number of L1210 cells with $IC_{50}\;of\;54.6\;{\mu}g/mL$ after 3 days culture, whereas little effect was observed against normal lymphocytes (<6% compared to 83.2% of L1210 cells under the same condition). Increased SOD and GPx enzyme activities, and remarkably augmented generation of ${O_2}^-$ ion in L1210 cells by E. japonicum extract, implied that reactive oxygen species including ${O_2}^-$ ion, might have participated in L1210 cell death

나물이나 전분원료로 사용되어 온 얼레지(Erythronium japonicum)의 항암작용을 검색하였다. 얼레지 추출물을 Sarcoma 180으로 복수암을 유발시킨 ICR 마우스에 대하여 경구투여 한 결과 143.7%에 이르는 생명연장효과를 얻었으며, 백혈병계 암세포인 L1210 세포에 대해서는 최고 98.6%의 세포수 감소효과를 얻었다. 아울러 얼레지 추출물의 독성유무를 검색하고자 normal lymphocyte를 분리하여 이 정상세포에 얼레지 추출물을 첨가했을 때 세포수 감소는 거의 일어나지 않았으며, 고농도의 3일간의 긴 배양기간에 의해서도 L1210 세포의 경우 83.2%에 비해 5.8% 정도로 매우 적었다. 이와 같은 결과로부터 얼레지 추출물은 무독성 또는 저독성 항암제로서의 개발 가치가 있을 것으로 사료되었다. 한편 얼레지 추출물의 암세포에 대한 작용 기작으로 일환으로 활성산소인 ${O_2}^-$의 생성량을 측정한 결과 control 값의 최대 약 3.6배까지 크게 증가하였으며, 동시에 ${O_2}^-$ 전환효소인 SOD와 SOD의 종산물인 $H_2O_2$, 분해효소인 GPx도 각각 5배와 3배까지 크게 증가하였다. 따라서 얼레지 추출물은 암세포에서 ${O_2}^-$를 비롯한 활성산소를 유발시키고 이 증가된 활성산소가 암세포의 apoptosis를 야기하는 것으로 간주되었다.



  1. Mullin WJ, Peacock S, Loewen DC, Turner NJ. Macronutrients content of yellow glacierlily and balsamroot; root vegetables used by indigenous peoples of north western north America. Food Res. Intl. 30: 769-775 (1997)
  2. Ritsena T, Smeekens M. Fructans: beneficial for plants and humans. Curr. Opin. Plant Biol. 6: 223-229 (2003)
  3. Cooper PD, Carter M. The anti-melanoma activity of inulin in mice. Mol. Immunol. 23: 903-911 (1986)
  4. Astrow AB. Rethinking cancer. Lancet 343: 494-503 (1994)
  5. Bailer JC, Gormick HL. Cancer undefeated. N. Eng. J. Med. 336: 1569-1575 (1997)
  6. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen species and nitrogen species in inflammatory disease and progression to cancer. Biochem. J. 313: 1729-1734 (1996)
  7. Evans MD, Griffith HR, Lunec J. Reactive oxygen species and their cytotoxic mechanisms. Adv Mol. Cell. Biol. 20: 25-31 (1997)
  8. Steel VE. Current mechanistic approaches to the chemoprevention of cancer. J. Biochem. Mol. Biol. 36: 78-81 (2003)
  9. Serrano J, Palmeria CM, Kuehl DW. Wallace KB. Cardioselctive and cumulative oxidation of mitochondrial DNA following subchromic doxoruicin administration. Biochem. Biophys. Acta 1411: 201-205 (1999)
  10. Reynolds CP, Maureer BJ. Kolesnick RN. Ceramide synthesis and metabolismas as target for cancer therapy. Cancer Lett. 206: 169 -180 (2004)
  11. Sould AK, Tacka KA, Galvan KA, Penefsky HS. Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem. Pharmacol. 66: 977-987 (2003)
  12. Boyum A. Isolation of leukocytes from human blood. Scan. J. Clin. Invest. 21: 9-15 (1968)
  13. Thayer PS, Himmelfarb P, Watts GI. Cytotoxicity assays with L1210 cells in vitro: Comparison with L1210 in vivo and KB cells in vitro. Cancer Chemother. Rep. (part 2) 2: 1-25 (1971)
  14. Markesbery WR. Oxidative stress hypothesis in Alzheimer disease. Free Rad. Biol. Med. 23: 134-139 (1994)
  15. McCord J, Fridovich I. Superoxide dismutase. An enzymatic function for erythrocuprein (heterocuprein). J. Biol. Chem. 244: 6049-6052 (1969)
  16. Maral J, Puget K, Michelson AM. Comparative study of superoxide dismutase, catalase, glutathione peroxidase levels in erythrocytes of different animals. Biochem. Biophys. Res. Comm. 77: 1525-1531 (1997)
  17. Reiter RJ. Oxidative processes and antioxidative defense mechanism in the aging brain. FASEB J. 9: 528-534 (1995)
  18. Amstad P, Moret R, Cerutti P. Glutathione peroxidase compensates for the hypersensativity of Cu-Zn superoxide dismutase overproducers to oxidant stress. J. Biol. Chem. 58: 1606-1612 (1994)
  19. Orrenius S. Mechanisms of Oxidative Cell Damage: An Overview of Oxidative Process and Antioxidants. Raven Press Ltd., New York, NY, USA. pp.53-71 (1994)