Skip to main content
SpringerLink
Log in

Camptothecin accumulation in various organ cultures of Camptotheca acuminata Decne grown in different culture systems

  • Original Paper
  • Published:
Plant Cell, Tissue and Organ Culture (PCTOC) Aims and scope Submit manuscript

Abstract

Levels of camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) were determined in different cultures of Camptotheca acuminata grown either in a Temporary Immersion System (TIS) or on solid medium. CPT was also detected in liquid culture medium. HPLC analysis showed significant differences in CPT contents in all tissues analysed and the highest CPT contents were found in shoots grown on solid medium and in TIS with a mean of 2.2 and 2.5 mg g−1 DW, respectively. The highest content of CPT detected in seedlings was 1.96 mg g−1 DW; while that of somatic embryos at cotyledonary stage and regenerated plants were 0.87 and 1.23 mg g−1 DW, respectively. It was also shown that shoots cultured in TIS secreted substantial amount of CPT into the liquid medium. After 4 weeks in culture a mean of 6, 05 and 12, 6 μg g−1 FW were determined at 4 and 8 immersion cycles daily (IC d−1), respectively. This aspect opens new possibilities regarding the isolation of CTP using TIS culture systems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abdelmohsen UR, Ali W, Eom SH, Hentschel U, Roitsch T (2010) Synthesis of distinctly different sets of antimicrobial activities by elicited plant cell suspension cultures. Plant Cell Tiss Organ Cult. doi:10.1007/s11240-010-9898-y

  • Abdullah MA, Ali AM, Marziah M, Lajis NH, Ariff AB (1998) Establishment of cell suspension cultures of Morinda elliptica for the production of anthraquinones. Plant Cell Tiss Org Cult 54:173–182

    Article  CAS  Google Scholar 

  • Aitken-Christie J (1991) Automation. In: Debergh PC, Zimmerman RH (eds) Micropropagation: technology and application. Kluwer Academic Publishers, Dordrecht, pp 363–388

    Google Scholar 

  • Amna T, Puri SC, Verma V, Sharma JP, Khajuria RK, Musarrat J, Spiteller M, Qazi GN (2006) Bioreactor studies on the endophytic fungus Entrophospora infrequens for the production of an anticancer alkaloid camptothecin. Can J Microbiol 52:189–196

    Article  PubMed  CAS  Google Scholar 

  • Arvy MP, Imbault N, Naudascher F, Thiersault M, Doireae P (1994) 2, 4-D and alkaloid accumulation in periwinkle cell suspensions. Biochimie 76:410–416

    Article  PubMed  CAS  Google Scholar 

  • Barrios-Gonzalez J, Fernandez FJ, Tomasini A, Mejia A (2005) Secondary metabolites production by solid-state fermentation. Malaysian J Microbiol 1:1–6

    Google Scholar 

  • Becker Y, Olshevsky U (1973) Inhibition of herpes simplex virus replication by camptothecin. lsr J Med Sci 9:1578–1581

    CAS  Google Scholar 

  • Bertin C, Yang X, Weston LA (2003) The role of root exudates and allelochemicals in the rhizosphere. Plant Soil 256:67–83

    Article  CAS  Google Scholar 

  • Bodley AL, Shapiro TA (1995) Molecular and cytotoxic effects of camptothecin, a topoisomerase I inhibitor, on trypanosomes and Leishmania. Proc Nat Acad Sci USA 92:3726–3730

    Article  PubMed  CAS  Google Scholar 

  • Ciddi V, Shuler ML (2000) Camptothecine from callus cultures of Nothapodytes foetida. Biotechnol Lett 22:129–132

    Article  CAS  Google Scholar 

  • Coste A, Vlase L, Halmagyi A, Deliu C, Coldea G (2011) Effects of plant growth regulators and elicitors on production of secondary metabolites in shoot cultures of Hypericum hirsutumand Hypericum maculatum. Plant Cell Tiss Organ Cult. doi:10.1007/s11240-011-9919-5

  • Cunningham D, Pyrhonen S, James RD, Punt CJ, Hickish TF, Heikkila R, Johannesen TB, Starkhammar H, Topham CA, Awad L, Jacques C, Herait P (1998) Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352:1413–1418

    Article  PubMed  CAS  Google Scholar 

  • Dakora FD, Phillips DA (2002) Root exudates as mediumtors of mineral acquisition in low-nutrient environments. Plant Soil 245:35–47

    Article  CAS  Google Scholar 

  • Douillard JY, Cunningham D, Rothm AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047

    Article  PubMed  CAS  Google Scholar 

  • El Tahchy A, Bordage S, Ptak A, Dupire F, Barre E, Guillou C, Henry M, Chapleur Y, Laurain-Mattar D (2011) Effects of sucrose and plant growth regulators on acetylcholinesterase inhibitory activity of alkaloids accumulated in shoot cultures of Amaryllidaceae. Cell Tiss Organ Cult. doi:10.1007/s11240-011-9933-7

  • Ewesuedo RB, Ratain MJ (1997) Topoisomerase I inhibitors. The Oncologist 2:359–364

    PubMed  CAS  Google Scholar 

  • Frankfater CR, Dowd MK, Triplett BA (2009) Effect of elicitors on the production of gossypol and methylated gossypol in cotton hairy roots. Plant Cell Tiss Organ Cult 98:341–349

    Article  CAS  Google Scholar 

  • Fulzele DP, Satdive RK (2003) Somatic embryogenesis, plant regeneration and the evaluation of the camptothecin content in Nothapodytes foetida. Soc In Vitro Biol 39:212–216

    CAS  Google Scholar 

  • Gurney KA, Evans LV, Robinson DS (1992) Purine alkaloid production and accumulation in cocoa callus and suspension cultures. J Exp Bot 43:769–775

    Article  CAS  Google Scholar 

  • Hawes MC, Bengough G, Cassab G, Ponce G (2003) Root caps and rhizosphere. J Plant Growth Regul 21:352–367

    Article  Google Scholar 

  • Hsiang Y, Hertzberg R, Hecht S, Liu LF (1985) Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 260:14873–14878

    PubMed  CAS  Google Scholar 

  • Imanishi S, Hashizume K, Nakakita M, Kojima H, Matsubayashi Y, Hashimoto T, Sakagami Y, Yamada Y, Nakamura K (1998) Differential induction by methyl jasmonate of genes encoding ornithine decarboxylase and other enzymes involved in nicotine biosynthesis in tobacco cell cultures. Plant Mol Biol 38:1101–1111

    Article  PubMed  CAS  Google Scholar 

  • Kelly DC, Avery RJ, Dimmock JN (1974) Carnptothecin: an inhibitor of influenza virus replication. J Gen Virol 25:427–432

    Article  PubMed  CAS  Google Scholar 

  • Kim TW, Innocenti F (2007) Insights, challenges, and future directions in irinogenetics. Ther Drug Monit 29:265–270

    Article  PubMed  Google Scholar 

  • Komaraiah P, Kavi Kishor PB, Carlsson M, Magnusson KE, Mandenius CF (2005) Enhancement of anthraquinone accumulation in Morinda citrifolia suspension cultures. Plant Sci 168:1337–1344

    Article  CAS  Google Scholar 

  • Li S, Yi Y, Wang Y, Zhang Z, Beasly RS (2002) Camptothecin accumulation and variations in Camptotheca. Planta Med 68:1010–1016

    Article  PubMed  CAS  Google Scholar 

  • Li S, Zhang Z, Cain A, Wang B, Long M, Taylor J (2005) Antifungal activity of camptothecin, trifolin, and hyperoside isolated from Camptotheca acuminata. J Agric Food Chem 53:32–37

    Article  PubMed  CAS  Google Scholar 

  • Liu ZJ (2000) Drought-induced in vivo synthesis of camptothecin in Camptotheca acuminata seedlings. Plant Physiol 11:483–488

    Google Scholar 

  • Liu WZ (2004) Secretory structures and their relationship to accumulation of camptothecin in Camptotheca acuminata (Nyssaceae). Acta Bot Sinica 46:1242–1248

    CAS  Google Scholar 

  • Liu Z, Carpenter SB, Bourgeois WJ, Yu Y, Constantin RJ, Falcon MJ, Adams JC (1998) Variations in the secondary metabolite camptothecin in relation to tissue age and season in Camptotheca acuminata. Tree Physiol 18:265–270

    PubMed  CAS  Google Scholar 

  • Liu Z, Zhou G, Xu S, Wu J, Yin Y (2002) Provenance variation in camptothecin concentrations of Camptotheca acuminata grown in China. New Forests 24:215–224

    Article  CAS  Google Scholar 

  • Lopez-Meyer M, Nessler CL, Mcknight TD (1994) Sites of accumulation of the antitumor alkaloid camptothecin in Camptotheca acuminata. Planta Med 60:558–560

    Article  PubMed  CAS  Google Scholar 

  • Lorence L, Nessler CL (2004) Camptothecin, over four decades of surprising findings. Phytochemistry 65:2735–2749

    Article  PubMed  CAS  Google Scholar 

  • Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RCAM, de Jong LA, Pluim D, Beijnen JH, Schellens JHM (2001) Circumvention of breast cancer resistance protein (BCRP)-mediumted resistance to camptothecins in Vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 7:935–941

    PubMed  CAS  Google Scholar 

  • Mooney HA, Winner WE, Pell EJ (1991) Response of plants to multiple stresses. Academic Press, San Diego

    Google Scholar 

  • Namdeo AG (2007) Plant cell elicitation for production of secondary metabolites. Pharmacogn Rev 1:69–79

    CAS  Google Scholar 

  • Nolte BA (1999) Micro-analysis and localization of camptothecin in Camptotheca acuminata. M.S. Thesis, Texas A&M University, College Station

  • Pan XW, Xu HH, Gao X, Liu X, Lu YT (2004a) Improvement of growth and camptothecin yield by altering nitrogen source supply in cell suspension cultures of Camptotheca acuminata. Biotechnol Lett 26:1745–1748

    Article  PubMed  CAS  Google Scholar 

  • Pan XW, Shi YY, Liu X, Gao X, Lu YT (2004b) Influence of inorganic microelements on the production of camptothecin with suspension cultures of Camptotheca acuminata. Plant Growth Regul 44:59–63

    Article  CAS  Google Scholar 

  • Park YG, Kim MH, Yang JK, Chung GY, Choi MS (2003) Light-susceptibility of camptothecin production from in vitro cultures of Camptotheca acuminata Decne. Biotechnol Bioprocess Eng 8:32–36

    Article  CAS  Google Scholar 

  • Pasqua G, Monacelli B, Valletta A (2004) Cellular localisation of the anti-cancer drug camptothecin in Camptotheca acuminata Decne (Nyssaceae). Eur J Histochem ISSN 1121-760X 48:321–328

    Google Scholar 

  • Pérez-Alonso N, Wilken D, Gerth A, Jähn A, Nitzsche HM, Kerns G, Capote-Perez A, Jiménez E (2009) Cardiotonic glycosides from biomass of Digitalis purpurea L. cultured in temporary immersion systems. Plant Cell Tiss Organ Cult 99:151–156

    Article  Google Scholar 

  • Priel E, Showalter SD, Blair DG (1991a) Inhibition of human immuno-deficiency virus (HIV-1) replication by non-cytotoxic doses of camptothecin, a topoisomerase I inhibitor. AIDS Res Hum Retroviruses 7:65–72

    PubMed  CAS  Google Scholar 

  • Priel E, Showalter SD, Roberts M, Oroszlan S, Blair DG (1991b) The topoisomerase I inhibitor, camptotbecin, inhibits equine infectious anemia virus replication in chronically infected CF2Th cells. J Virol 65:4137–4141

    PubMed  CAS  Google Scholar 

  • Rhee HS, Cho HY, Son SY, Yoon SYH, Park JM (2010) Enhanced accumulation of decursin and decursinol angelate in root cultures and intact roots of Angelica gigas Nakai following elicitation. Plant Cell Tiss Organ Cult 101:295–302

    Article  CAS  Google Scholar 

  • Roja G, Heble MR (1994) The quinoline alkaloids camptothecin and 9-methoxy camptothecin from tissue cultures and mature trees of Nothapodytes foetida. Phytochemistry 36:65–66

    Article  CAS  Google Scholar 

  • Sakato K, Misawa M (1974) Effects of chemical and physical condition of growth of Camptotheca acuminata cell culture. Arg Biol Chem 38:491–497

    CAS  Google Scholar 

  • Sankar-Thomas YD, Saare-Surminski K, Lieberei R (2008) Plant regeneration via somatic embryogenesis of Camptotheca acuminata in temporary immersion system (TIS). Plant Cell Tiss Org Cult 95:163–173

    Article  Google Scholar 

  • Sudo H, Hasegawa Y, Matsunaga J (1991) Jpn. Pat. 03 272 628

  • Valletta A, Santamaria AR, Pasqua G (2007) CPT accumulation in the fruit and during early phases of plant development in Camptotheca acuminata Decaisne (Nyssaceae). Nat Prod Res 21:1248–1255

    Article  PubMed  CAS  Google Scholar 

  • Van-Hengel AJ, Harkes MP, Wichers HJ, Hesselink PGM, Buitelaar RM (1992) Characterization of callus formation and camptothecin production by cell lines of Camptotheca acuminata. Plant Cell Tiss Org Cult 28:11–18

    Article  CAS  Google Scholar 

  • Van Hengel AJ, Buitelaar RM, Wichers HJ (1994) Camptotheca acuminata Decne: in vitro culture and the production of camptothecin. In: Bajaj YPS (ed) Biotechnology in agriculture and forestry, vol 28. Medicinal and aromatic plants VII. Springer, Berlin, pp 98–112

    Google Scholar 

  • Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA (1966) Plant antitumor agents. I. Isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 88:3888–3890

    Article  CAS  Google Scholar 

  • Wiedenfeld H, Furmanowa M, Roeder E, Guzewska J, Gustowski W (1997) Camptothecin and 10-hydroxycamptothecin in callus and plantlets of Camptotheca acuminata. Plant Cell Tiss Org Cult 49:213–218

    Article  CAS  Google Scholar 

  • Yeoman MM, Miedzybrodzka MB, Lindsey K, McLauchlan WR (1980) The synthetic potential of cultured plant cells. In: Sala F, Parisi B, Cella R, Cifferi O (eds) Plant cell cult: results and perspectives. Elsevier-North Holland, Amsterdam, pp 327–343

    Google Scholar 

  • Yeoman MM, Lindsey K, Hall RD (1982a) Differentiation as a prerequisite for the production of secondary nretabolites. In: Proceedings of plant cell culture conference, Sudbury House, London, pp 1–7. Oyez Scientific and Technical Services Ltd, London

  • Yeoman MM, Miedzybrodzka MB, McLauchlan WR (1982b) Accumulation of secondary products as a facet of differentiation in plant cell and tissue cultures. In: Yeoman MM, Truman DES (eds) Differentiation in vitro. British Society for cell biology symposium, vol 4. Cambridge University Press, Cambridge, pp 65–82

    Google Scholar 

  • Yuan Y, Liu Z, Yang Y, Wu H (2008) Studies on the production of comptothecin in in vitro cultured roots of Camptotheca acuminata. In: The 2nd international conference on bioinformatics and biomedical engineering (iCBBE 2008)

  • Zhang J, Yu Y, Liu D, Liu Z (2007) Extraction and composition of three naturally occurring anti-cancer alkaloids in Camptotheca acuminata seed and leaf extracts. Phytomedicine 14:50–56

    Article  PubMed  Google Scholar 

  • Zu Y, Tang Z, Yu J, Liu S, Wang W, Guo X (2003) Different responses of camptothecin and 10-hydroxycamptothecin to heat shock in Camptotheca acuminata seedlings. J Integrative Plant Biol 7:809–814

    Google Scholar 

Download references

Acknowledgments

The authors thanks Dr. Mechthild Jonas Seattle Genetics, Inc. Bothell, WA 98021, USA; Dr. Douglas A. Steinmacher, UFSC, Universidade Federal de Santa Catarina, Programa de Po′s Graduac¸a˜o em Recursos Gene′ticos Vegetais-CCA, 88040-900 Florianópolis, SC, Brazil and Mike Cummins (BA) Concentration and History University of Athabasca for their critical reading and comments on this manuscript.

Author information

Authors and Affiliations

  1. Department of Crop Science and Plant Ecology, Biocentre Klein Flottbek and Botanical Garden, Ohnhorststr. 18, 22609, Hamburg, Germany

    Yantree Devi Sankar-Thomas & Reinhard Lieberei

Authors
  1. Yantree Devi Sankar-Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reinhard Lieberei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yantree Devi Sankar-Thomas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sankar-Thomas, Y.D., Lieberei, R. Camptothecin accumulation in various organ cultures of Camptotheca acuminata Decne grown in different culture systems. Plant Cell Tiss Organ Cult 106, 445–454 (2011). https://doi.org/10.1007/s11240-011-9942-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11240-011-9942-6

Keywords

Search

Navigation