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The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Role of Sp in the Regulation of Notch1 Gene Expression by Curcumin

커큐민에 의한 노치발현 조절에서 Sp의 역할

  • Park, Seon-Yeong (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Kang, Yong-Gyu (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Bae, Yun-Hee (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Kim, Su-Ryun (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Park, Hyun-Joo (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Kang, Young-Soon (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Kim, Mi-Kyoung (Department of Oral Physiology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Wee, Hee-Jun (Department of Biochemistry, College of Pharmacy, Seoul National University) ;
  • Jang, Hye-Ock (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Bae, Moon-Kyoung (Department of Oral Physiology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Woo, Jae Suk (Department of Physiology, School of Medicine, Yangsan Campus of Pusan National University) ;
  • Bae, Soo-Kyung (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University)
  • 박선영 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 강용규 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 배윤희 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 김수륜 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 박현주 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 강영순 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 김미경 (부산대학교 치의학전문대학원 구강생리학교실) ;
  • 위희준 (서울대학교 약학대학 생화학교실) ;
  • 장혜옥 (부산대학교 치의학전문대학원 치과약리학교실) ;
  • 배문경 (부산대학교 치의학전문대학원 구강생리학교실) ;
  • 우재석 (부산대학교 의학전문대학원 생리학교실) ;
  • 배수경 (부산대학교 치의학전문대학원 치과약리학교실)
  • Received : 2012.11.15
  • Accepted : 2012.12.12
  • Published : 2013.02.27
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Abstract

Curcumin has diverse anticancer activities that lead to tumor growth inhibition of cancer cells and induction of apoptosis. Curcumin is involved in the regulation of multiple genes via transcription factors including NF-${\kappa}B$, STATs, AP1, and SP. Notch signaling plays critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thereby may contribute to the development of various cancers involving breast cancer. This study was to investigate the effects of curcumin on Notch1 gene expression and to explore the underlying mechanism. Here, we found that curcumin decreased the levels of Notch1 mRNA and protein in MDA-MB-231 human breast cancer cells, along with the downregulation of Sp family genes (Sp1, Sp2, Sp3, and Sp4). The repressive effect of curcumin on Notch1 gene transcription was confirmed by performing Notch1 promoter-driven reporter assay and three Sp-binding sites were identified on Notch1 promoter that may act as curcumin-respose elements. Moreover, treatment with mitramycin A, a specific Sp inhibitor, decreased the levels of Notch1 mRNA and protein in human breast cancer cells. Taken together, our results indicate that Notch1 gene expression is downregulated by curcumin, at least in part, through the suppression of Sp family, which may lead to apoptosis in human breast cancer cells.

Keywords

References

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