Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
권호 표지

Cadmium Induces Apoptosis Through Oxidative Stress in Human Breast Cancer MCF-7 Cells

인간 유방암 세포 MCF-7에서 산화적 스트레스에 의한 카드뮴의 아폽토시스

  • 오지영 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 이수정 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 신재호 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 김태성 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 문현주 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 강일현 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 강태석 (식품의약품안전청 국립독성연구원 내분비장애물질과) ;
  • 김안근 (숙명여자대학교 약학대학) ;
  • 한순영 (식품의약품안전청 국립독성연구원 내분비장애물질과)
  • Published : 2004.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

본 연구는 건전지나 플라스틱 등 산업물질, 식품, 흡연 그리고 공기, 물 등을 통해 인간과 생태계에 노출되고 있는 중금속 카드뮴을 인간 유방암 세포 MCF-7에 처리하였을 때 일어나는 현상을 살펴보고 나아가 카드뮴의 독성기전을 규명하기 위해 시행되었다. 카드뮴으로 인한 아폽토시스는 DNA분절 현상과 핵의 쪼개짐, 세포주기에 있어서 sub-G1의 출현 그리고 아폼토시스시에 발현되는 단백질 caspase의 발현, 특히 산화적 스트레스상태에서 마이토콘드리아가 손상을 입었을 때 발현되는 caspase-9의 발현을 통해 확인하였다. 카드뮴으로 인한 산화적 스트레스는 활성 산소종이 대조군에 비해 증가하고 이를 방어하기 위한 항산화효소 superofide dismutase, catalase, glutathion redurtase가 감소함을 통하여 확인하였다. 이 상의 결과들을 통해 카드뮴은 인간 유방암 세포 MCF-7에서 산화적 스트레스를 유발시켜 아폼토시스를 일으키는 것으로 추정할 수 있다.

Keywords

References

  1. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-126 https://doi.org/10.1016/S0076-6879(84)05016-3
  2. Beyersmann D and Hechtenberg S. Cadmium, gene regulation and cellular signaling in mammalian cells, Toxicol Appl Pharmacol 1997; 144: 247-261 https://doi.org/10.1006/taap.1997.8125
  3. Bonnefoy M, Drai J and Kostka T. Antioxidants to slow aging, facts and perspectives, Presse Med 2002; 31: 1174-1184
  4. Carmody RJ and Cotter TG. Signaling apoptosis: a radical approach, Redox Rep 2001; 6: 77-90 https://doi.org/10.1179/135100001101536085
  5. David LS, Robert DG and Leslie AL. Cells. Cold Spring Harbor Laboratory Press 1997; Vol. 1. Detmar Beysersmann. Effects of carcinogenic metals on gene expression, Toxicol letters 2002; 127: 63-68 https://doi.org/10.1016/S0378-4274(01)00484-2
  6. El Azzouzi B, Tsangaris GT, Pellegrini O, Manuel Y, Benveniste J and Thomas Y. Cadmium induces apoptosis in a human T cell line, Toxicology 1994; 88: 127-139 https://doi.org/10.1016/0300-483X(94)90115-5
  7. Elinos-Baez CM, Maldonado V, Melendez-Zajgla J. Caspases: apoptosis inducing molecules, Gac Med Mex 2003;139: 493-499
  8. Farris MW. Cadmium toxicity: unique cytoprotective properties of alpha tocopheryl succinate in hepatocytes, Toxicology 1991; 69: 63-77 https://doi.org/10.1016/0300-483X(91)90154-S
  9. Fleury C, Mignotte B, Vayssiere JL. Mitochondrial reactive oxygen species in the cell death signaling, Biochimie 2002; 84(2-3): 131-141 https://doi.org/10.1016/S0300-9084(02)01369-X
  10. Garcia-Alfonso C, Martinez-Galisteo E, Llobell A, Barcena JA and Lopez-Barea J. Horse-liver glutathione reductase: purification and characterization, Int J Biochem 1993; 25: 61-68 https://doi.org/10.1016/0020-711X(93)90490-6
  11. Habeebu SS, Liu J, Klaassen CD. Cadmium-induced apoptosis in mouse liver, Toxicol Appl Pharmacol 1998; 149: 203-209 https://doi.org/10.1006/taap.1997.8334
  12. Hamada T, Sasaguri T, Tanimoto A, Arima N, Shimajiri S, Abe T and Sasaguri Y. Apoptosis of human kidney 293 cells is promoted by polymerized cadmium-metallothionein, Biochem Biophys Res Commun 1996; 219: 829-834 https://doi.org/10.1006/bbrc.1996.0318
  13. Hart BA, Lee CH, Shukla GG, Shukla A, Osier M, Eneman JD and Chiu JF. Characterization of cadmium-induced apoptosis in rat lung epithelial cells: evidence for the participation of oxidant stress, Toxicology 1999; 133: 43-58 https://doi.org/10.1016/S0300-483X(99)00013-X
  14. Hartwig A. Role of DNA repair inhibition in lead and cadmium-induced genotoxicity: a review, Environ Health Persp ect 1994; 102: 45-50
  15. Hartwig A and Beyersmann D. Comutagenicity and inhibition of DNA repair by metal ions in mammalian cells, Biol. Trace Elements Res 1989; 21: 359-365 https://doi.org/10.1007/BF02917276
  16. Hussein T, Shulka GS and Chandra SF. Effects of cadmium on superoxide dismutase and lipid peroxidation in liver and kidney of growing rats: in vivo and in vitro studies, Pharmacol Toxicol 1987; 60: 355-358 https://doi.org/10.1111/j.1600-0773.1987.tb01526.x
  17. Jiang ZY, Woollard AC and Wolff SP. Lipid hydroperoxide measurement by oxidation of $Fe^{2+}$ in the presence of xylenol orange. Comparison with the TBA assay and an iodometric method, Lipids 1991; 26: 853-856 https://doi.org/10.1007/BF02536169
  18. Julio EC. Cell biology (2nd edition) Academic press 1994; Vol. 1
  19. Koizumi T, Yokota T, Shirakura H., Tatsumoto H and Suzuki KT. Potential mechanism of cadmium-induced cytotoxicity in rat hepatocytes: Inhibitory action of cadmium on mitochondrial respiratory activity, Toxicology 1994; 92: 115-125 https://doi.org/10.1016/0300-483X(94)90171-6
  20. Kumar D and Jugdutt BI. Apoptosis and oxidants in the heart, J Lab Clin Med 2003; 142: 288-297 https://doi.org/10.1016/S0022-2143(03)00148-3
  21. Li M, Kondo T, Zhao L, Li FJ, Tanabe K, Arai Y, Zhou ZC and Kasuya M. Apoptosis induced by cadmium in human lymphoma U937 cells through $Ca^{2+}$-calpain and caspase-mitochondria-dependent pathways, J Biol Chem 2000; 275: 39702-39709 https://doi.org/10.1074/jbc.M007369200
  22. Manca D, Richard AC, Trottier B and Chevalier G. Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride, Toxicology 1991; 67: 303-323 https://doi.org/10.1016/0300-483X(91)90030-5
  23. Mates JM, Perez-Gomez C and Nunez de Castro I. Antioxidant enzymes and human diseases, Clin Biochem 1999; 32: 595-603 https://doi.org/10.1016/S0009-9120(99)00075-2
  24. Matsuoka M and Call KM. Cadmium-induced expression of immediate early genes in LLC-PK1 cells, Kidney Int 1995; 48: 383-389 https://doi.org/10.1038/ki.1995.306
  25. Nebot C, Moutet M, Huet P, Xu JZ, Yadan JC and Chaudiere J. Spectrophotometric assay of superoxide dismutase activity based on the activated autoxidation of a tetracyclic catechol, Anal Biochem 1993; 214: 442-451 https://doi.org/10.1006/abio.1993.1521
  26. Owuor ED and Kong AN. Antioxidants and oxidants regulated signal trasduction pathways, Biochem Pharmacol 2002; 64: 765-770 https://doi.org/10.1016/S0006-2952(02)01137-1
  27. Pryor WA. Oxy-radicals and related species: their formation, lifetimes and reactions, Annu Rev Physiol 1986; 48: 657-667 https://doi.org/10.1146/annurev.ph.48.030186.003301
  28. Stacey NH, Cantilena Jr LR and Klaassen CD. Cadmium toxicity and lipid peroxidation in isolated rat hepatocytes, Toxicol Appl Pharmacol 1980; 53: 470-480 https://doi.org/10.1016/0041-008X(80)90359-2
  29. Stohs S and Bagchi D. Oxidative mechanisms in the toxicity of metal ions, Free Radical Bol Med 1995. 18: 321-336 https://doi.org/10.1016/0891-5849(94)00159-H
  30. Thornberry NA and Lazebnik Y. Caspase: enemies within, Science 1998; 281: 1312-1316 https://doi.org/10.1126/science.281.5381.1312
  31. Tsangaris GT and Tzortzatou-Stathopoulou F. Cadmium induces apoptosis differentially on immune system cell lines, Toxicology 1998; 128: 143-150 https://doi.org/10.1016/S0300-483X(98)00032-8
  32. Wakimoto M, Masuoka N, Nakano T and Ubuka T. Determination of glutathione peroxidase activity and its contribution to hydrogen peroxide removal in erythrocytes, Acta Med Okayama 1998; 52: 233-237
  33. Yu RA and Chen XM. Effects of selenium on rat hepato cellular DNA damage, apoptosis and changes of cell cycle induced by cadmium in vivo, Zhonghua Yu Fang Yi Xue Za Zhi 2004; 38(3): 155-158
  34. Zheng H, Liu J, Choo K, Michalska AE and Klaassen CD. Metallothionein-I and -II knock out mice are sensitive to cadmium-induced liver mRNA expression of c-jun and p53, Toxicol Appl Pharmacol 1996; 136: 229-235 https://doi.org/10.1006/taap.1996.0029