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(β-lapachone Regulates Tight Junction Proteins, Claudin-3 and -4, in Human Hepatocarcinoma Cells.

인체 간암세포에서 β-lapachone 처리에 의한 Tight Junction 관련 유전자의 변화

  • Kim, Sung-Ok (Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School) ;
  • Kwon, Jae-Im (Department of Biochemistry, Dongeui University Graduate School) ;
  • Kim, Gi-Young (Faculty of Applied Marine Science, Cheju National University) ;
  • Kim, Nam-Deuk (Division of Pharmacy (BK21 Program), Pusan National University) ;
  • Choi, Yung-Hyun (Department of Biomaterial Control (BK21 Program), Department of Biochemistry, Dongeui University Graduate School)
  • 김성옥 (동의대학교 대학원 바이오물질제어학과(BK21 Program)) ;
  • 권재임 (동의대학교 한의과대학 생화학교실) ;
  • 김기영 (제주대학교 해양과학대학) ;
  • 김남득 (부산대학교 약학대학 약학과) ;
  • 최영현 (동의대학교 대학원 바이오물질제어학과(BK21 Program), 한의과대학 생화학교실)
  • Published : 2007.09.30

Abstract

A hallmark of cancers is 'leaky' tight junctions (Tjs). TJs mediated paracellular permeability is elevated and TJs maintained cell polarity is frequently lost. Concomitantly, TJs-associated proteins including members of the claudin family of proteins are dysregulated. Recent findings indicate that these TJs changes can contribute to cancer progression. In this study, we examined the effects of ${\beta}-lapachone$, a quinone compound obtained from the bark of the lapacho tree (Tabebuia avellanedae), on the Tjs-associated regulators in human hepatocarcinoma cell lines, HepG2 and Hep3B. ${\beta}-lapachone$ treatment downregulated the levels of insulin-like growth factor 1 receptor (IGF-lR) proteins in both HepG2 and Hep3B cells. But the levels of claudin-3 and -4 proteins were increased in ${\beta}-lapachone$-treated HepG2 and Hep3B cells. And also the zonnula occludens-l (la-I) and p-catenin protein levels by ${\beta}-lapachone$ were increased in a time-dependent manner. However, claudin-3 and -4 mRNA levels were uninhibited by ${\beta}-lapachone$ in HepG2 and Hep3B. The present results suggest that the upregulation of claudin-3 and -4 protein levels by ${\beta}-lapachone$ occurs by a post-transcriptional mechanism and points to a novel mechanism by ${\beta}-lapachone$.

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