Environmental Mutagens and Carcinogens (한국환경성돌연변이발암원학회지)

Korean Environmental Mutagen Society (한국환경성돌연변이발암원학회)
권호 표지

Study on the Estrogen Receptor Mediated Toxicity of Cadmium and Protective Effects of Antioxidant

에스트로겐 수용체를 통한 카드뮴 독성 및 항산화제에 의한 독성경감에 관한 연구

  • Kim Tae-Sung (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Kang Tae-Seok (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Kang Ho-Il (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Moon Hyun-Ju (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Kang Il-Hyun (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Lee Young-Joo (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Choi Eun-Hee (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Hong Jin-Tae (College of Pharmacy, Chungbuk National University) ;
  • Han Soon-Young (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA) ;
  • Hong Jin-Hwan (Department of Toxicological Research Team of Endcrine Toxicology National Institute of Toxicological Research, KFDA)
  • 김태성 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 강태석 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 강호일 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 문현주 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 강일현 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 이영주 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 최은희 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 홍진태 (충북대학교 약학대학) ;
  • 한순영 (국립독성연구원 독성연구부 내분비장애물질팀) ;
  • 홍진환 (국립독성연구원 독성연구부 내분비장애물질팀)
  • Published : 2006.03.01
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Abstract

Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells: MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = $50\;{\mu}M$ at MCF-7 cells and $120{\mu}M$ at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium ($100{\mu}M$) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and $ER{\alpha}$.

Keywords

References

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