Effect of Genistein on the Aryl Hydrocarbon Receptor and Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells

인체유방암 세포주 MCF-7 세포에서 genistein의 Aryl Hydrocarbon Receptor와 Cytochrome P450 1A1에 대한 영향

  • Han Eun-Hee (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University) ;
  • Kim Ji-Young (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University) ;
  • Jeong Hye-Gwang (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
  • Published : 2006.03.01

Abstract

화학적 예방효과가 있는 식물성 에스트로젠은 다양한 환성을 나타내며 여러 세포 수용체와 상호작용한다. Genistein은 isoflavone의 주요물질 중의 하나로 콩류에 존재하며 대표적인 식물성 에스트로젠이다. 본 논문에서는 유방암 세포주인 MCF-7에서 aryl hydrocarbon receptor(AhR)에 의해 매개되는 발암물질 활성화 경로에 대한 genistein의 영향을 살펴보았다. 세포에 genistein을 처리할 경우 cytochrome P450 1A1(CYP1A1) 약물대사효소의 특이적인 효소반응인 7-ethoxyresorufin O-deethylase (EROD) 활성도와 CYP1A1의 유전자 발현이 genistein의 농도 의존적으로 증가하였다. Genistein과 발암물질인 방향족탄화 수소 7, 12-dimethylbenz[a]anthracene(DMBA)를 동시 처리하였을 경우 DMBA에 의해 유도되어 증가된 EROD활성도와 CYP1A1의 유전자 발현이 genistein에 의해 감소하였다. 랫트의 간에서 분리한 세포질을 이용하여 genistein과 AhR의 대표적인 ligand인 2,3,7,8-tetrachlorodibenzo-p-dioxin과 경쟁적 결합에 대한 영향을 조사한 결과 genistein이 AhR에 경쟁적으로 결합함을 알 수 있었다. 이러한 결과들은 genistein이 천연 AhR ligand임을 암시한다. 따라서, 식물성 에스트로젠인 genistein은 AhR경로의 길항제/항진제로 작용할 수 있을 것으로 사료된다.

Keywords

References

  1. Brotons JA, Olea-Serrano MF, Villalobos M, Pedraza, V and Olea N. Xenoestrogens released from lacquer coatings in food cans. Environ Health Perspect 1995; 103: 608-612 https://doi.org/10.2307/3432439
  2. Cho H, Yun CW, Park WK, Kong JY, Kim KS, Park Y, Lee S and Kim BK. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives, Pharmacol Res 2004; 49: 37-43 https://doi.org/10.1016/S1043-6618(03)00248-2
  3. Chomczynski P and Sacchi N. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156-159
  4. Cos P, De BT, Apers S, Vanden BD, Pieters L and Vlietinck, AJ. Phytoestrogens: recent developments. Planta Med 2003; 69: 589-599 https://doi.org/10.1055/s-2003-41122
  5. Denison, MS, Vella LM and Okey AB. Structure and function of the Ah receptor for 2, 3, 7, $8-tetrachlorodibenzo-{\rho}-dioxin$. Species difference in molecular properties of the receptors from mouse and rat hepatic cytosols. J Biol Chem 1986; 261: 3987-39958
  6. Dipple A. Reactions of polycyclic aromatic hydrocarbon carcinogens. IARC Sci Publ 1994; 125: 107-129
  7. Gasiewicz TA and Neal RA. The examination and quantitation of tissue cytosolic receptors for 2, 3, 7, $8-tetrachlorodibenzo-{\rho}-dioxin$ using hydroxylapatite. Anal Biochem 1982; 124: 1-11 https://doi.org/10.1016/0003-2697(82)90212-3
  8. Hankinson O. The aryl hydrocarbon receptor complex. Annu. Rev Pharmacol Toxicol 1995; 35: 307-340 https://doi.org/10.1146/annurev.pa.35.040195.001515
  9. Hollman PC and Katan MB. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother 1997; 51: 305-310 https://doi.org/10.1016/S0753-3322(97)88045-6
  10. Jeong HG, Lee SS, Kim HK and Yang KH. Murine Cyp1a-1 induction in mouse hepatoma Hepa-1C1C7 cells by myristicin. Biochem Biophys Res Commun 1997; 28: 619-622
  11. Juchau MR. Substrate specificities and functions of the P450 cytochromes. Life Sci 1990; 47: 2385-2394 https://doi.org/10.1016/0024-3205(90)90482-7
  12. Krishnan V, Porter W, Santostefano M, Wang X and Safe S. Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2, 3, 7, $8-tetrachlorodibenzo-{\rho}-dioxin$ (TCDD) in MCF-7 cells. Mol Cell Biol 1995; 15: 6710-9 https://doi.org/10.1128/MCB.15.12.6710
  13. MacDonald CJ, Ciolino HP and Yeh GC. Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of cytochromes P50 1A1, 1A2, and 1B1. Cancer Res 2001; 61: 3919-39242-282
  14. McDougal A, Wilson C and Safe S. Inhibition of 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumor growth by aryl hydrocarbon receptor agonists. Cancer Lett 1997; 120: 53-63 https://doi.org/10.1016/S0304-3835(97)00299-1
  15. Olea N, Pulgar R, Perez P, Olea-Serrano F, Rivas A, Novillo-Fertrell A, Pedraza V, Soto AM and Sonnenschein C. Estrogenicity of resin-based composites and sealants used in dentistry. Environ Health Perspect 1996; 104: 298-305 https://doi.org/10.2307/3432888
  16. Rowell C, Carpenter DM and Lamartiniere CA. Chemoprevention of breast cancer, proteomic discovery of genistein action in the rat mammary gland. J Nutr 2005; 135: 2953-2959S8
  17. Taioli E. International collaborative study on genetic susceptibility to environmental carcinogens. Cancer Epidemiol Biomarkers Prev 1999; 8: 727-728