Synthetic Chenodeoxycholic Acid Derivative HS-1200-Induced Apoptosis of Human Oral Squamous Carcinoma Cells

합성 Chenodeoxycholic Acid 유도체 HS-1200이 유도한 사람구강 편평상피암종세포 세포자멸사 연구

  • Kim, In-Ryoung (Department of Biology, College of Natural Science, Pusan National University) ;
  • Sohn, Hyeon-Jin (Department of Oral Anatomy, College of Dentistry, Pusan National University) ;
  • Kim, Gyoo-Cheon (Department of Oral Anatomy, College of Dentistry, Pusan National University) ;
  • Kwak, Hyun-Ho (Department of Oral Anatomy, College of Dentistry, Pusan National University) ;
  • Park, Bong-Soo (Department of Oral Anatomy, College of Dentistry, Pusan National University) ;
  • Choi, Won-Chul (Department of Biology, College of Natural Science, Pusan National University) ;
  • Ko, Myung-Yun (Department of Oral Medicine, College of Dentistry, Pusan National University) ;
  • Ahn, Yong-Woo (Department of Oral Medicine, College of Dentistry, Pusan National University)
  • 김인령 (부산대학교 자연과학대학 생물학과) ;
  • 손현진 (부산대학교 치과대학 구강해부학교실) ;
  • 곽현호 (부산대학교 치과대학 구강해부학교실) ;
  • 김규천 (부산대학교 치과대학 구강해부학교실) ;
  • 박봉수 (부산대학교 치과대학 구강해부학교실) ;
  • 최원철 (부산대학교 자연과학대학 생물학과) ;
  • 고명연 (부산대학교 치과대학 구강내과학교실) ;
  • 안용우 (부산대학교 치과대학 구강내과학교실)
  • Published : 2007.09.30

Abstract

Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Previous studies have been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis inducing activity on various cancer cells in vitro. It wasn't discovered those materials have apoptosis induced effects on YD9 human oral squamous carcinoma cells. The present study was done to examine the synthetic bile acid derivatives(HS-1199, HS-1200) induced apoptosis on YD9 cells and such these apoptosis events. We administered them in culture to YD9 cells. Tested YD9 cells showed several lines of apoptotic manifestation such as activation of caspase-3, degradation of DFF, production of poly (ADP-ribose) polymerase(PARP) cleavage(HS-1200 only), DNA degradation(HS-1200 only), nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential(HS-1200 only) and the release of cytochrome c and AIF to cytosol. Between two synthetic CDCA derivatives, HS-1200 showed stronger apoptosis-inducing effect than HS-1199. Therefore HS-1200 was demonstrated to have the most efficient antitumor effect. Taken collectively, we demonstrated that a synthetic CDCA derivative HS-1200 induced caspases-dependent apoptosis via mitochondrial pathway in human oral sqauamous carcinoma cells in vitro. Our data therefore provide the possibility that HS-1200 could be considered as a novel therapeutic strategy for human orall squamous carcinoma from its poweful apoptosis-inducing activity.

담즙산과 합성담즙산유도체가 여러 종류의 암세포에 세포자멸사(apoptosis)를 유도하고 항암효과가 있다고 알려져 있다. 합성 chenodeoxycholic acid (CDCA) 유도체가 여러 가지 암세포에 유도한 세포자멸사 in vitro 연구들이 보고되어져 왔다. 하지만 아직 까지 구강편평상피암종세포에 합성 CDCA 유도체가 유도한 세포자멸사 연구는 없었다. 그래서 본 연구는 합성 CDCA 유도체인 HS-1199와 HS-1200이 사람구강편평상피암종세포에 세포자멸사 효과와 세포자멸사 기작을 알기 위해서 수행되었다. 합성 CDCA 유도체로 처리된 사람구강편평상피암종세포(YD9 세포)에서 caspase-3의 활성화, DFF의 degradation, poly (ADP-ribose) polymerase(PARP)의 분절화(HS-1200 only), DNA 분절화(HS-1200 only), 핵 응축, proteosome 활성화의 저해, 사립체막전위 (MMP)의 감소(HS-1200 only) 그리고 cytochrome c와 AIF의 사립체에서 세포질로의 유리와 같은 세포자멸사의 증거를 보였다. 그리고 두 개의 합성 CDCA 유도체 중에서 HS-1200이 HS-1199보다 더욱 더 강한 세포자멸사 효과를 보였다. 이 결과는 HS-1200이 YD9 세포에 항암효과를 가진다는 것을 증명한 것이다. 본 연구는 CDCA 유도체인 HS-1200이 사람구강편평상피암종세포에서 사립체 경로를 통한 caspase 의존적 세포자멸사를 강력하게 유도한다는 것을 증명했으며, 이러한 결과는 HS-1200이 사람구강편평상피암종의 치료적 전략으로서의 가능성이 높다고 생각한다.

Keywords

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