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인간 전립선 암세포인 TSU-Pr1에서 trans-10,cis-12 Conjugated Linoleic Acid에 의한 Apoptosis 유발과 Bcl-2 단백질의 발현억제

Induction of Apoptotic Cell Death and Depression of Bcl-2 Protein Levels by Trans-10,cis-12 Conjugated Linoleic Acid in Human Prostate Cancer

  • 오윤신 (한림대학교 식품영양학과) ;
  • 김은지 (한림대학교 식품영양학과) ;
  • 이상곤 (한림대학교 비뇨기과) ;
  • 정차권 (한림대학교 식품영양학과) ;
  • 강일준 (한림대학교 식품영양학과) ;
  • 신현경 (한림대학교 식품영양학과) ;
  • 윤정한 (한림대학교 식품영양학과)
  • 발행 : 2002.12.01

초록

CLA 이성체 mixture와 trans-10,cis-12 CLA는 살아있는 TSU-Prl 세포 수를 감소시키는 반면 LA와 cis-9,trans-11 CLA는 세포 수에 아무런 효과가 없었다. 세포 수를 감소시키는 CLA 이성체 mixture와 tran-10, cis-12 CLA는 apoptotic cell death를 유도하는 것을 관찰하였고, 특히 trans-10,cis-12 CLA는 Bcl-2/Bax 비율을 감소시켰다. Trans-10,cis-12 CLA에 의해 Bax와 Bcl-2 mRNA의 수준이 변하지 않았으므로 이 지방산에 의한 Bcl-2의 변화는 mRNA 전사 후에 일어나는 단계에서 일어난다고 결론지을 수 있다. 이로써 CLA에 의한 세포증식 억제는 부분적으로 TSU-Prl 세포의 apoptosis를 유도함으로서 이루어지는 것이라 할 수 있다.

Conjugated linoleic acid (CLA) is a collective term for a class of positional and geometric conjugated dienoic isomers of linoleic acid (LA) and has anti-cancer activity in experimental animals. We have previously observed that an isomeric mixture of CLA and trans-10,cis-12 (t10c12) inhibited cell growth in a dose-dependent manner whereas LA and cis-9,trans-11 (c9t11) had no effect. The present study examined whether the CLA mixture and t10c12 induce apoptotic cell death. TSU-Prl cells were incubated for three days in serum-free medium in the absence or presence of individual fatty acids, and the DNA fragmentation assay was performed. Cells treated with the CLA mixture or t10c12 produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. By contrast, LA and c9t11 had no effect. Western immunoblot analysis of total lysates revealed that t10c12 reduced anti-apoptotic, 26 kDa, Bcl-2 protein levels by 49$\pm$8% compared with controls, whereas this CLA isomer did not alter pro-apoptotic,21 kDa, Bax protein levels. These results suggest that growth inhibitory effect of the t10c12 CLA isomer may, at least in part, be attributed to Increased apoptotic death in TSU-Prl cells.

키워드

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피인용 문헌

  1. trans-10,cis-12 Conjugated Linoleic Acid Inhibits Insulin-Like Growth Factor-I Receptor Signaling in TSU-Pr1 Human Bladder Cancer Cells vol.13, pp.1, 2010, https://doi.org/10.1089/jmf.2009.1201
  2. -12 Conjugated Linoleic Acid Induces Depolarization of Mitochondrial Membranes in HT-29 Human Colon Cancer Cells: A Possible Mechanism for Induction of Apoptosis vol.12, pp.5, 2009, https://doi.org/10.1089/jmf.2009.0056