Abstract
The glucosylation of the cytotoxic lignan podophyllotoxin by cell cultures derived from Linum flavum was investigated. Four cyclodextrins: β-cyclodextrin, γ-cyclodextrin, dimethyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin were used to improve the solubility of podophyllotoxin by complexation. Dimethyl-β-cyclodextrin met our needs the best and the solubility of podophyllotoxin could be enhanced from 0.15 to 1.92 mM, using a podophyllotoxin/cyclodextrin ratio of 1:1. Growth parameters of the cell suspensions were not affected neither by the addition of cyclodextrins alone, nor when complexed podophyllotoxin was dissolved in the medium.
The complexed lignan disappeared rapidly from the culture medium, within 24h, under all experimental conditions. Almost simultaneously, between 73 and 100% of detectable podophyllotoxin was bioconverted into podophyllotoxin-β-d-glucoside. A maximal bioconversion rate of 0.51 mmol l-1 suspension day-1 was calculated for the L. flavum cells growing in a medium which included the podophyllotoxin/dimethyl-β-cyclodextrin complex at a final concentration of 1.35 mM.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alfermann AW, Schuller J & Reinhard E (1980) Biotransformation of cardiac glycosides by immobilized cells of Digitalis lanata. Planta Med. 40: 218–223
Berlin J, Wray V, Mollenschott C & Sasse F (1986) Formation of β-peltatin-A-methylether and coniferin by root cultures of Linum flavum. J. Nat. Prod. 49: 435–439
Berlin J, Bedorf N, Mollenschott C, Wray V, Sasse F & Höfle G (1988) On the podophyllotoxins of root cultures of Linum flavum. Planta Med. 54: 204–206
Broomhead AJ & Dewick PM (1990) Aryltetralin lignans from Linum flavum and Linum capitatum. Phytochemistry 29: 3839–3844
Buchardt O, Boe Jensen R, Hansen HF, Nielsen PE, Andersen D & Chinoin J (1986) Thermal chemistry of podophyllotoxin in ethanol and a comparison of the cytostatic activity of the thermolysis products. J. Pharm. Sci. 75: 1076–1080
Döller PC, Alfermann AW & Reinhard E (1977) Biotransformation of cardenolides by cell suspension cultures of Digitalis lanata and Thevetia neriifolia. Planta Med. 31: 1–6
Duchêne D & Wouessidjewe D (1990a) Physicochemical characteristics and pharmaceutical uses of cyclodextrin derivatives, Part I. Pharm. Technol. 1 (6) 26–34
Duchêne D & Wouessidjewe D (1990b) Physicochemical characteristics and pharmaceutical uses of cyclodextrin derivatives, Part II. Pharm. Technol. 14 (8) 22–30
Forsey SP, Rajapahsa D, Taylor NJ & Rodrigo R (1989) Comprehensive synthetic route to eight diastereomeric Podophyllum lignans. J. Org. Chem. 54: 4280–4290
Furya T (1978) Biotransformation by plant cell cultures. In: Thorpe TA (Ed) Frontiers of plant tissue culture (pp 191–200), Univ. of Calgary Press, Calgary
Hösel W (1981) The Biochemistry of Plants, Vol 7 (pp 725–753). Academic Press, New York
Kreis W, May U & Reinhard E (1986) UDP-glucose: digitoxin 16'-O-glucosyltransferase from suspension-cultured Digitalis lanata cells. Plant Cell Rep. 5: 442–445
Lewinsohn E, Berman E, Mazur Y & Gressel S (1986) Glucosylation of exogenous flavanones by grapefruit (Citrus paradisi) cell cultures. Phytochemistry 25: 2531–2535
Mizukami H, Terao T, Miura H & Ohashi H (1983) Glycosylation of salicyl alcohol in cultured plant cells. Phytochemistry 22: 679–680
Mizukami H, Terao T, Amano A & Ohashi H (1986) Glucosylation of salicyl alcohol by Gardenia jasminoides cell cultures. Plant Cell Physiol. 27: 645–650
Pras N (1992) Bioconversion of naturally occurring precursors and related synthetic compounds using plant cell cultures: a review. J. Biotechnol. (in press)
Scholten HJ, Schans MJ & Somhorst IPM (1991) Factors affecting the glucosylation capacity of cell cultures of Datura innoxia and Scopolia carniolica for monophenolic compounds. Plant Cell Tiss. Org. Cult. 26: 173–178
Tabata M, Ikeda F, Hiraoka N & Konoshima M (1976) Glucosylation of phenolic compounds by Datura innoxia suspension cultures. Phytochemistry 15: 1225–1229
Tabata M, Umetani Y, Shima K & Tanaka S (1984) Glucosylation of esculetin plant cell suspension cultures. Plant Cell Tiss. Org. Cult. 3: 3–9
Tabata M, Umetani Y, Ooya M & Tanaka S (1988) Glucosylation of phenolic compounds by plant cell cultures. Phytochemistry 27: 809–813
Van Uden W, Pras N, Vossebeld EM, Mol JNM & Malingré ThM (1990) Production of 5-methoxypodophyllotoxin in cell suspension cultures of Linum flavum L. Plant Cell Tiss. Org. Cult. 20: 81–87
Van Uden W, Pras N, Batterman S, Visser JF & Malingré ThM (1991a) The accumulation and isolation of coniferin from a high-producing cell suspension of Linum flavum L. Planta 183: 25–30
Van Uden W, Pras N, Homan B & Malingré ThM (1991b) Improvement of the production of 5-methoxypodo-phyllotoxin using a new selected root culture of Linum flavum L. Plant Cell Tiss. Org. Cult. 27: 115–121
Van Uden W, Homan B, Woerdenbag HJ, Pras N, Malingré ThM, Wichers HJ & Harkes M (1992) Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum. J. Nat. Prod. 55: 102–110
Wichers HJ, Harkes MP & Arroo RJ (1990) Occurrence of 5-methoxypodophyllotoxin in plants, cell cultures and regenerated plants of Linum flavum. Plant Cell Tiss. Org. Cult. 23: 93–100
Wichers HJ, Versluis-De Haan GG, Marsman JW & Harkes MP (1991) Podophyllotoxins in plants and cell cultures of Linum flavum. Phytochemistry 30: 3601–3604
Woerdenbag HJ, Pras N, Frijlink HW, Lerk CF & Malingré ThM (1990a) Cyclodextrin-facilitated bioconversion of 17β-estradiol by a phenoloxidase from Mucuna pruriens cell cultures. Phytochemistry 29: 1551–1554
Woerdenbag HJ, Van Uden W, Frijlink HW, Lerk CF, Pras N & Malingré ThM (1990b) Increased podophyllotoxin production in Podophyllum hexandrum cell suspension cultures after feeding coniferyl alcohol as a β-cyclodextrin complex. Plant Cell Rep. 9: 97–100
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
van Uden, W., Oeij, H., Woerdenbag, H.J. et al. Glucosylation of cyclodextrin-complexed podophyllotoxin by cell cultures of Linum flavum L.. Plant Cell Tiss Organ Cult 34, 169–175 (1993). https://doi.org/10.1007/BF00036098
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00036098