Enhanced Production of Anticancer Agent Camptothecin by Double Elicitors in Suspension cultures of Camptotheca acuminata

희수[Camptotheca acuminata] 현탁세포배양에서 복합 Elicitor에 의한 항암제 Camptothecin 생산 촉진

  • Choi, Hoon (School of Chemical Engineering and Biotechnology, College of Engineering, Ajou University) ;
  • Byun, Sang-Yo (School of Chemical Engineering and Biotechnology, College of Engineering, Ajou University)
  • 최훈 (아주대학교 공과대학 화학·생물공학부) ;
  • 변상요 (아주대학교 공과대학 화학.생물공학부)
  • Published : 2000.10.01

Abstract

Cell cultures of Camptotheca acuminata, which is known to produce the anticancer indole alkaloid camptothecin and its dervatives, were made to enhance the productivity of camptothecin. In suspension cultures, the maximum cell growth rate in exponential growth phase was $0.269day^{-1}$ which was correlated to 2.58days of cell doubling time. The production of camptothecin was non-growth associated. The camptothecin production was the highest at 11th day form inoculation and then it decreased. Various elicitors were applied to enhance the production of camptothecin. Both of jasmonic acid and cellulase increased the production of camptothecin. The optimal dosing time of elicitor was the beginning of the cultures. The combination of two elicitors was more effective to produce camptothecin than single applications. $20.42{\times}10^{-3}mg/\ell$ of camptothecin was obtained with combined application of two elicitors in two days.

희수 (Camptotheca acuminata) 현닥세포배양에서 최근 항암 제로서 관심을 팔고있는 camptothecin을 얻기 위하여 연구를 수행하였다. 현탁세포배양에서 exponential phase의 최고 생장 속도는 $0.269day^{-1}$이었으며 배가시간이 2.58일이었다. Camptothecin 은 배양초기에 생성되지 않고 exponential phase 말기부터 서서히 생성되어 stationary phase 초기에 최고를 나타내고 이후 급격히 감소하였다. Camptothecin의 생산을 촉진하기 위하여 elicitor를 사F용하였다. 여러 elicitor 중 jasmonic acid와 cellulase 가 camptothecin의 생성을 증가시켰다, Elicitor는 접종과 동시 에 투여 했을 때 가장 효과가 좋았으며, jasmonic acid와 cellulase 의 combination으로 효과가 더욱 증진했는데 대조구에 비하여 약 20배 정도 증가한 $20.42{\times}10^{-3}mg/\ell$ 의 camptothecin이 생 성되었다. 이것은 생산량을 증가시킨 것뿐만 아니라 생산기 간도 약 1/4로 단축시키는 결과를 얻을 수 있었다.

Keywords

References

  1. Plant Cell. Tissue and Organ Culture v.28 Characterization of callus and camptothecin production by cell lines of Camptotheca acuminata Hengel, A. J.;M. P. Harkes;H. J. Wichers;P. G. M. Hesselink;R. M. Buitelaar
  2. Technical Bulletin no.1415 Camptotheca acuminata Decaisne(Nyssaceae), source of camptothecin, an antileukemic alkaloid Predue, R. E.;R. L. Smith;M. E. Wall;J. L. Hartwell;B. J. Abbott
  3. Trends Biotechnol. v.3 The potential role of immobilization in plant cell biotechnology Brodelius, P.
  4. Biotechnol. Agre. Forest. v.26 Anchusa officinalis : Production of rosmarinic acid in perfusion cell culture Su, W. W.;E. C. Asali;A. E. Humphrey
  5. J. Microbiol. Biotechnol. v.8 no.6 Characterization of cell growth and camptothecin production in cell cultures of Camptotheca acuminata Song, S. H.;S. Y. Byun
  6. Cancer Research v.55 Camptothecin and Taxol : Discovery to Clinic-Thirteenth Bruce F. Cain in Memorial Award Lecture Wall. M. E.;M. C. Wani
  7. Ph. D. thesis, Dept. of Chem. Eng. Rutgers Studies on elicitation and In-situ recovery of alkaloids in suspension cultures of California Poppy Byun, S. Y.
  8. MS thesis, Dept of Biotechnology Studies on the production enhancement of (10-deacetyl) baccatin Ⅲ and paclitaxel in suspension cultures of Taxus baccata Pendula Moon. W. J.
  9. Planta Med. v.6 Improvement of diogenin yield from Dioscorea deltoidea plant cell cultures by use of non-traditinal hydrolysis method Drapeau D.;Y. Sauvaire;H. W. Blanch;C. R. White
  10. J. Plant Physiol. v.142 12-Oxo-phytodiencoic acid induces accumulation of berberine bridge enyme transcript in a manner analogous to methyl jasmonate Kutchan, T.
  11. Proc. Natl. Acad. Sci. U. S. A. v.89 Jasmonic acid is a signal transducer in elicitor-induced plant cell cultures Gundlach, H.;M. Muuler;T. Kutchan;M. Zenk
  12. MS thesis Studies on the cold precipitation of apple juice Kim, S. S.
  13. MS thesis Pectinase - characteristics of the pectinase produced by Aspergilus aureus L. Park, J. S.
  14. MS thesis Studies on the production of anticancer agent camptothecin and its derivatives in cell cultures Camptotheca acuminata Song, S. H.