Purification and Biological Activities of MT 1155 Inducing Morphological Change of Rous Sarcoma Virus-Transformed Normal Rat Kidney Cell

Rous Sarcoma Virus에 의해 형질전환된 NRK 세포의 형태변화를 유도하는 활성물질 MT 1154의 분리와 생물학적 활성

  • 안종석 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 박문수 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 박찬선 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 윤병대 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 민태익 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 안순철 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 오원근 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 이현선 (한국과학기술연구원 유전공학연구소 미생물공학연구실) ;
  • 윤병대 (한국과학기술연구원 유전공학연구소 미생물공학연구실)
  • Published : 1993.02.01

Abstract

We isolated Actinomycetes strain GMT 1155 and purified the active compound, MT 1155, on the morphological reversion of ts/NRK cell from the isolate. MT 1155 was identified as toyocamycin having antifungal and antitumor activities from physico-chemical properties and UV, IR, $^1H$-NMR, $^13C$-NMR and mass spectrum. MT 1155 showed the morphologically reversional activity on ts/NRK cell and the cytotoxicity on CTLL cell at the final concentrations of 1.7 JlM and 0.2 11M, respectively and its $IC_{50}$ value on protein kinase A enzyme was 2.3 $\mu$M. Also it had strong antifungal activity against several pathogenic fungi but not antibacterial activity. And it did not inhibit both protein kinase C activity and the bleb-formation of K562 cell induced by phorbol esters.

방선균 분리주 GMT 1153로부터 ts/NRK 세포의 형태를 변형된 세포형태에서 정상세포의 형태로 전환하는 활성물질을 분리, 정제하였다. 활성물질 MT 1155는 UV, IR, 1H-NMR, 13C-NMR, mass,원소분석 등의 기기분석을 통하여 항진균성 항암물질인 toyocamycin으로 동정되었다. MT 1155는 ts/NRK 세포의 형태전환에 대한 활성외에도 PKA 효소활성 저해와 CTLL 세포에 대한 세포독성이 있으나 K562 소포형성 억제 및 PKC 효소활성에 대한 저해효과도 없었다.

Keywords

References

  1. Cell v.64 Molecular themes in oncogenesis Bishop,J.M.
  2. Tips v.121 Signalling targets for anticancer drug development Powis,G.
  3. Molecullar & Cellular Biology v.6 Phenotypic change from transformed to normal induced by benzoquinoid ansamycins accompanies inactivation of $p60^ {src}$ in rat kidney cells infected with Rous sarcoma virus Uehara,Y.;M.Hori;T.Takeuchi;H.Umezawa
  4. Jpn. J. Cancer. Res. v.76 Screening of agents which convert transformed morphology of Rous sarcoma virus-infected rat kidney cells to normal morphology: Identification of an active agent as herbimycin and its inhibition of intracellular src kinase Uehara,Y.;M.Hori
  5. J. Antibiot. v.45 Inhibition of tyrosine kinases and src oncogene functions by stable erbstatin analogues Hori,T.;T.Kondo;T.Tsuji;M.Inoto;K.Umezawa
  6. J. Nat. Prod. v.52 Isolation of a novel tyrosine kinase inhibitor, lavendustin A. from Streptomyces griseolavendus Onoda,T.;H.Iinuma;Y.Sasaki;M.Hamada;T.Takeuchi;K.Umezawa
  7. J. Biol. Chem. v.262 Genistein, a specific inhibitor of tyrosine-specific protein kinases Akiyama,T.;J.Ishida;S.Nakagawa;H.Ogawara;S.Watanabe;N.Itoh;M.Shibuya;Y.Fukami
  8. 산업미생물학회지 v.20 방선균 분리주 No. 1882-5로부터 Phorbol Ester에 의해 유도되는 K562 cell의 소포형성을 억제하는 물질의 분리와 동정 안종석;안순철;이현선;박문수;오원근;김보연;민태익
  9. J. Biol. Chem. v.263 Biochemical characterization of rat brain protein kinase C isozymes Huang,K.P.;F.L.Huang;H.Nakabayashi;Y.Yoshida
  10. Biochem. Biophys. Res. Commun. v.135 Staurosporine a potent inhibitor of phospholipid/$Ca^ {2+}$ dependent protein kinase Tamaoki,T.;H.Nomoto;I.Takahashi;Y.Kato;M.Morimoto;F.Tomita
  11. J. Biol. Chem. v.251 Comparison of mode of activation of guanosine 3'.5'-monophosphate-dependent and adenosine 3'.5'-monophosphate-dependent protein kinases from silk worm Takai,Y.;S.Nagaya;M.Inoue;A.Kishimoto;K.Nishiyama;H.Yamamura;Y.Nishizuka
  12. J. Immunol. Methods v.117 A method for the quantitation of interleukin-2 activity Hewlett,G.;K.G.Stunkel;H.D.Schlumberger
  13. J. Antibiot. v.44 Herbicidal nucleosides from microbial sources Isaac,B.G.;S.W.Ayer;L.J.Letendre;R.J.Stonard
  14. Tetrahedron Letters v.24 The structure of a novel nucleoside antibiotic, dapiramycin A Seto,H.;N.Koyama;H.Ogine;Y.Kodama
  15. J. Antibiot. Ser. v.A8 Antibiotics from Streptomyces sp. No. E212 I Kikuchi,K.
  16. J. Am. Chem. Soci. v.91 Pyrrolopyrimidine nucleosides, Ⅲ. The total synthesis of toyocamycin. sangivamycin, tubercidin and related derivatives Tolman,R.L.;R.K.Robins;L.B.Townsend
  17. J. Antibiot. v.39 A specific inhibitor for tyrosine protein kinase from Pseudomonas Ogawara,H.;T.Akiyama;J.Ishida;S.Watanabe;K.Suzuki
  18. J. Antibiot. v.44 Reveromucin A, a new antibiotic which inhibits the mitogenic activity of epidermal growth factor Osada,H.;H.Koshino;K.Isono
  19. J. Antibiot. v.43 Inhibition of phosphatidylinositol kinase by toyocamycin Nishioka,H.;T.Sawa;M.Hamada;N.Shimura;M.Imoto;K.Umezawa
  20. J. Antibiot. v.42 A new biological role of sangivamycin: Inhibition of protein kinases Osada,H.;T.Sonoda;K.Tsunoda;K.Isono
  21. J. Antibiot. v.42 Induction by herbimycin A of contact inhibition in v-src-expressed cells Uehara,Y.;Y.Moriya;M.Hori;T.Takeuchi
  22. J. Biol. Chem. v.263 Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C Loomis,C.R.;R.M.Bell
  23. J. Immunol. v.147 IL-2 binding activates a tyrosine-phosphorylated phosphatidylinositol-3-kinase Merida,I.;E.Diez;G.N.Gaulton
  24. FEBS v.279 Induction of morphological change by tyrosine kinase inhibitors in Rous sarcoma virus-transformed rat kidney cells Umezawa,K.;K.Tanaka;T.Hori;S.Abe;R.Sekizawa;M.Imoto
  25. J. Antibiot. v.41 Nucleoside antibiotics: Structure biological activity and biosynthesis Isono,K.