Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
권호 표지

Synthetic Bile Acid Derivative HS-1200-induced Apoptosis of Human Osteosarcoma Cells

합성담즙산유도체가 유도한 뼈육종세포 세포자멸사 연구

Kim, Gyoo-Cheon;Her, Young-Soo;Park, Jae-Hyun;Moon, Yong-Suk;Yoo, Yeong-Hyun;Shin, Sang-Hun;Park, Bong-Soo
김규천;허용수;박재현;문용석;유영현;신상훈;박봉수

  • Published : 20041000
⟨ Previous Next ⟩

Abstract

Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and had anticancer effects. However, it wasn’t discovered those materials have apoptosis induced effects on osteosarcoma cells. The present study was done to examine the synthetic bile acid derivatives induced apoptosis on osteosarcoma cells and such these apoptosis events. The synthetic bile acid derivatives, chenodeoxycholic acid (CDCA) induced the cell death on human osteosarcoma (HOS) cells contrary to ursodeoxycholic acid (UDCA). HS-1200, a synthetic derivative of CDCAs, was chosen to experiment apoptosis events in HOS cells. HOS cells treated with HS-1200 showed nucleus condensation, cytochrom c release, Bax/Bcl-xL alteration, activation of caspase-3 and caspase-activated deoxyribonuclease (CAD), and degradation of poly (ADP-ribose) polymerase (PARP). Though this study needs more investigations, these in vitro data suggest that treatment of the synthetic bile acid derivatives can give medical therapy on HOS cells.

담즙산 및 합성유도체가 여러 암세포에서 세포자멸사를 유도하여 항암활성을 보인다고 밝혀졌지만 뼈육종세포에서의 세포자멸사 유도활성은 보고된 바 없다. 본 연구는 담즙산 유도체들이 뼈육종세포에 세포자멸사를 유도하는지를 알아보고 그기작을 연구하기 위하여 수행되었다. UDCA 합성 유도체와는 달리 CDCA 합성유도체는 뼈육종세포의 사망을 유도하였다. CDCA 유도체 중 HS-1200을 선택하여 세포자멸사 기전을 연구하였다. HS-1200은 핵의 농축, cytochrome c 방출, Bax/Bcl-xL분율 변화, caspase-3의 활성화 및 CAD와 PARP 분절 등을 관찰되었다. 비록 더 많은 연구가 필요하지만 본 시험관 연구 자료는 합성담즙산 유도체 투여가 뼈육종의 치료전략이 될 수 있음을 시사한다.

Keywords

References

  1. Baek JH, Kim J, Kang C, Lee YS, Kim KW : Induction of apoptosis by bile acids in HepG2 human hepatocellular carcinoma cells, Korean J Physiol Pharmacol 1: 107-115, 1997
  2. Berger NA : Poly (ADP-ribose) polymerase in the cellular response to DNA damage, Radiat Res 101: 4-15, 1985
  3. Bossy-Wetzel E, Newmeyer DD, Green DR : Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization, EMBO J 17: 37-49, 1998
  4. Choi YH, Im EO, Suh H, Jin Y, Lee WH, Yoo YH, Kim KW, Kim ND : Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases, Int J Oncol 18: 979-984, 2001
  5. Cohen GM : Caspases: the executioners of apoptosis, Biochem J 326:1-16, 1997
  6. Fellenberg J, Mau H, Nedel S, Ewerbeck V, Debatin KM : Druginduced apoptosis in osteosarcoma cell lines is mediated by caspase activation independent of CD95-receptor/ligand interaction, J Orthop Res 18: 10-17, 2000
  7. Geen DR, Reed JC : Mitochondria and apoptosis, Science 281:1309-1312, 1998
  8. Heiskanen KM, Bhat MB, Wang HW, Ma J, Nieminen AL : Mitochondrial depolarization accompanies cytochrome c release during apoptosis in PC6 cells, J Biol Chem 274: 5654-5658, 1999
  9. Im EO, Choi YH, Paik KJ, Suh H, Jun Y, Kim KW, Yoo YH, Kim ND : Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells, Cancer Lett 163: 83-93, 2001
  10. Im EO, Lee S, Suh H, Kim KW, Bae YT, Kim ND : A novel ursodeoxycholic acid derivative induces apoptosis in human MCF-7 breast cancer cells, Pharm Pharmacol Commun 5: 1-6, 1999
  11. Kim DK, Lee JR, Kim A, Lee A, Yoo MA, Kim KW, Kim ND, Suh H : Inhibition of initiation of simian virus 40 DNA replication in vitro by the ursodexocycholic acid and its derivatives, Cancer Lett 146: 147-153, 1999 https://doi.org/10.1016/S0304-3835(99)00251-7
  12. Konopleva M, Zhao S, Xie Z, Segall H, Younes A, Claxton DF, Estrov Z, Kornblau SM, Andreeff M : Apoptosis. Molecules and mechanisms., Adv Exp Med Biol 457: 217-236, 1999
  13. Kroemer G, Zamzami N, Susin SA : Mitochondrial control of apoptosis, Immunol Today 18: 44-51, 1997
  14. Kroemer G, Dallaporta B, Resche-Rigon M : The mitochondrial death/life regulator in apoptosis and necrosis, Annu Rev Physiol 60: 619-642, 1998
  15. Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC : Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE, Nature 371: 346-347, 1994
  16. Lu Y, Yagi T : Apoptosis of human tumor cells by chemotherapeutic anthracyclines is enhanced by Bax overexpression, J Radiat Res (Tokyo) 40: 263-272, 1999
  17. Martinez JD, Stratagoules ED, LaRue JM, Powell AA, Gause PR, Craven MT, Payne CM, Powell MB, Gerner EW, Earnest DL : Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation, Nutr Cancer 31: 111-118, 1998
  18. Matsukawa Y, Marui N, Sakai T, Satomi Y, Yoshida M, Matsumoto K, Nishino H, Aoike A : Genistein arrests cell cycle progression at G2-M, Cancer Res 53: 1328-1331, 1993
  19. Neamati N, Fernandez A, Wright S, Kiefer J, McConkey DJ : Degradation of lamin B1 precedes oligonucleosomal DNA fragmentation in apoptotic thymocytes and isolated thymocyte nuclei, J Immunol 154: 3788-3795, 1995
  20. Oberhammer FA, Hochegger K, Froschl G, Tiefenbacher R, Pavelka M : Chromatin condensation during apoptosis in accompanied by degradation of lamin A${\pm}$B, without enhanced activation of cdc2 kinase, J Cell Biol 126: 827-837, 1994
  21. Park YH, Kim J, Baek J, Jung E, Kim T, Suh H, Park MH, Kim KW : Induction of apoptosis in HepG2 human hepatocellular carcinoma cells by a novel derivative of ursodeoxycholic acid (UDCA), Arch Pharm Res 20: 29-33, 1997 https://doi.org/10.1007/BF02974038
  22. Reed JC : Cytochrome c: can’t live with it--can’t live without it, Cell 91: 559-562, 1997
  23. Rosen A, Casciola-Rosen L : Macromolecular substrates for the ICE-like proteases during apoptosis, J Cell Biochem 64: 50-54, 1997
  24. Seki K, Yoshikawa H, Shiiki K, Hamada Y, Akamatsu N, Tasaka K : Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma, Cancer Chemother Pharmacol 45: 199-206, 2000
  25. Seo SY, Jun EJ, Jung SM, Kim KH, Lim YJ, Park BS, Kim JK, Lee S, Suh H, Kim ND, Yoo YH : Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin, Anticancer Drugs 14: 219-225, 2003
  26. Suh H, Jung EJ, Kim TH, Lee HY, Park YH, Kim KW : Anti-angiogenic activity of ursodeoxycholic acid and its derivatives, Cancer Lett 113: 117-122, 1997
  27. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G : Molecular characterization of mitochondrial apoptosis- inducing factor, Nature 397: 441-446, 1999
  28. Thomberry NA and Lazebnik Y : Caspase: enemies within, Science 281: 1312-1316, 1998
  29. Vaux DL, Korsmeyer SJ : Cell death in development, Cell 96: 245-254, 1999
  30. Williams GT : Programmed cell death: apoptosis and oncogenesis, Cell 65: 1097-1098, 1991
  31. Wyllie AH, Kerr JFR, Currie AR : Cell death: the significance of apoptosis, Int Rev Cytol 68: 251-305, 1980
  32. Yerushalmi B, Dahl R, Devereaux MW, Gumpricht E, Sokol RJ : Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition, Hepatology 33: 616-626, 2001
  33. Yuan J : Evolutionary conservation of a genetic pathway of programmed cell death, J Cell Biochem 60: 4-11, 1996
  34. Zou H, Li Y, Liu X, Wang X : An APAF-1, cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9, J Biol Chem 274: 11549-11556, 1999