Effects of 3,5-di-O-Caffeoylquinic acid from Artemisia scoparia Waldstein et Kitamura on the Function of HPV 16 Oncoproteins

인진에서 분리한 3,5-di-O-Caffeoylquinic acid가 자궁경부암 바이러스 발암단백질의 기능에 미치는 영향

  • Baek, Tae-Woong (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Kyung-Ae (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ahn, Min-Jung (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Joo, Hae-Kyung (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Min-Chul (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kang, Jung-Woo (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Hee-Seo (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Shim, Jung-Hyun (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hee-Gu (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Hyun-Cheol (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ahn, Jong-Seok (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Yong-Kwen (Department of Healthscience and Biochemistry, Changwon National University) ;
  • Myung, Pyung-Keun (Department of Pharmacy, College of Pharmacy Chungnam National University) ;
  • Yoon, Do-Young (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology)
  • 백태웅 (한국생명공학연구원 세포생물학연구실) ;
  • 이경애 (한국생명공학연구원 세포생물학연구실) ;
  • 안민정 (한국생명공학연구원 세포생물학연구실) ;
  • 주혜경 (한국생명공학연구원 세포생물학연구실) ;
  • 조민철 (한국생명공학연구원 세포생물학연구실) ;
  • 강정우 (한국생명공학연구원 세포생물학연구실) ;
  • 김희서 (한국생명공학연구원 세포생물학연구실) ;
  • 심정현 (한국생명공학연구원 세포생물학연구실) ;
  • 이희구 (한국생명공학연구원 세포생물학연구실) ;
  • 오현철 (한국생명공학연구원 세포생물학연구실) ;
  • 안종석 (한국생명공학연구원 세포생물학연구실) ;
  • 조용권 (창원대학교 보건생화학과) ;
  • 명평근 (충남대학교 약학과) ;
  • 윤도영 (한국생명공학연구원 세포생물학연구실)
  • Published : 2004.12.30

Abstract

Cervical cancer is one of the leading causes of female death. Viral oncoproteins E6 and E7 are selectively retained and expressed in carcinoma cells infected with HPV (Human papillomavirus) type 16. The HPV is cooperated in immotalization and transformation of primary keratinocyte. E6 and E7 oncoproteins interfere the functions of tumor suppressor proteins p53 and retinoblasoma protein (pRb), respectively. Among a lots of natural products, Artemisia scoparia Waldstein et Kitamura has inhibitory effects on the binding between E6 oncoprotein and tumor suppressor p53, or the binding between E6 and E6 associated protein (E6AP), an E3 ubiquitin-protein ligase. HPV oncoprotein inhibitors from Artemisia scoparia W. were isolated by solvent partition and column chromatography (Silica gel, RP-18) and the inhibitory compounds were finally purified by HPLC using an ELISA screening system based on the binding between E6 and E6AP. The aim of this study is to identify the structure of inhibitory compounds and to investigate whether these compounds have inhibitory effects on the functions of E6 oncoprotein. We investigated whether 3,5-di-O-caffeoylquinic acid (DCQA) extracted from Artemisia scoparia W. Could inhibit the function of E6 oncoprutein. DCQA inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53 and also inhibited the proliferation of human cervical cancer cell lines (SiHa and CaSKi) in a dose response manner. These results suggest that DCQA inhibited the function of E6 oncoprotein, suggesting that it can be used as a potential drug for the treatment of cervical cancers infected with HPV.

Keywords

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