Toxicological Research

  • 제19권2호
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  • Pages.91-98
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  • 2003
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지

인체 전립선 암세포에서 Alkylating Agent인 N-methyl-N'-nitro- N-nitrosoguanidine에 의한 Apoptosis유발

Induction of Apoptosis by N-methyl-N'-nitro-N-nitrosoguanidine, an Alkylating Agent, in Human Prostate Carcinoma Cells

  • 박철 (동의대학교 한의과대학 생화학교실, 부산대학교 자연과학대학 생물학과) ;
  • 최병태 (동의대학교 한의과대학 해부학교실 및 한의학연구소) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실)
  • Park, Cheol (Department of Biochemistry, Dong-Eui University College of Oriental Medicine, and Research Institute of Oriental Medicine, Department of Biology, Busan National University) ;
  • Choi, Byung-Tae (Department of Anatomy, Dong-Eui University College of Oriental Medicine and Research Institute of Oriental Medicine) ;
  • Lee, Won-Ho (Department of Biology, Busan National University) ;
  • Choi, Yung-Hyun (Department of Biochemistry, Dong-Eui University College of Oriental Medicine, and Research Institute of Oriental Medicine)
  • 발행 : 2003.06.01
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초록

Alkylating agents form alkylated base adducts in the DNA and cause DNA lesions leading to cell killing. In this study, we investigated the mechanism of apoptosis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in PC-3 and DU145 human prostate carcinoma cell lines. MNNG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner to a similar extent in both cell lines. This anti-proliferative effect of PC-3 and DU145 cells by MNNG was associated with morphological changed such as membrane shrinking, cell rounding up and formation of apoptotic bodies. MNNG treatment also induced a proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase (PARP) and $\beta$-catenin proteins in DU145 cells but in PC-3 cells. Furthermore, we observed an increase of proapoptotic protein Bax family expression and a decrease of antiapoptotic protein Bcl-2 family by MNNG treatment in a concentration-dependent manner MNNG also induced a proteolytic activation of caspase-3 and -9, which is believed to play a central role in the apoptotic signaling pathway.

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