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Plant Cell Cultures as Producers of Secondary Metabolites: Podophyllum Lignans as a Model

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Transgenesis and Secondary Metabolism

Abstract

Podophyllums have been used extensively as medicinal plants and are part of the folklore in Asian and American cultures. Their use dates back to the Chinese culture of 2,000 years ago where they were used as an antitumor drug. The resin podophyllin was first recommended as an antiviral agent and provided clues for new applications. The most important secondary metabolite isolated from the rhizomes and roots of the Podophyllum species is podophyllotoxin and its related lignans. This lignan is the precursor of the semisynthetic drugs etoposide, teniposide, and etopophos, which are clinically used in the therapeutic treatment of cancer. Moreover, other derivatives have shown different types of biological activity. With an increasing worldwide market for anticancer drugs, supplies of podophyllotoxin for the pharmaceutical industry are under great pressure. As the chemical synthesis of podophyllotoxin is not economic on a commercial scale, supplies are still obtained from wild populations of Podophyllum. Concern has been expressed about the shortage of Podophyllum which is now an endangered species due to overexploitation and a lack of cultivation. Attempts to increase plant yields have improved through in vitro technology while the production of podophyllotoxin will require further studies. This chapter provides an overview of the Podophyllum species and its lignans. Podophyllum biotechnology still presents challenges to be overcome and some of these are, in part, discussed in this chapter.

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Abbreviations

2,4-D:

2,4-Dichlorophenoxyacetic acid

AChE:

Acetylcholinesterase enzyme

B5:

Gamborg medium (1968)

BAP:

6-Benzylaminopurine

CAD:

Cinnamyl alcohol-dehydrogenase

CCC:

Countercurrent chromatography

cv:

Cultivar

CYP:

Cytochrome P450 enzymes

d. wt:

Dried weight

DEPBG:

4′-Demethylepipodophyllotoxin-d-benzylidene glucoside

DIR:

Dirigent protein

gusA :

β-Glucuronidase reporter gene

HPTLC:

High-performance TLC

HSV-I:

Herpes simplex virus type-1

HSV-II:

Herpes simplex virus type-2

IAA:

Indole-3-acetic acid

IUCN:

International Union for Conservation of Nature

LD50:

Lethal dose 50

MCMV:

Murine cytomegalovirus

MS:

Murashige and Skoog medium (1962)

NAA:

1-Naphthaleneacetic acid

NAD:

Nicotinamide adenine dinucleotide

NP-CC:

Normal-phase column chromatography

npt II :

Neomycin phosphotransferase gene

PAL:

Phenylalanine ammonium liase

PDA:

Photodiode array

PLR:

Pinoresinol–lariciresinol reductase

PTLC:

Preparative thin-layer chromatography

RP-HPLC:

Reversed-phase high-performance liquid chromatography

SAR:

Structure–activity relationship

SIRD:

Secoisolariciresinol dehydrogenase

TLC:

Thin-layer chromatography

UDP:

Uridine diphosphate

UPLC:

Ultra-performance liquid chromatography

UV–vis:

Ultraviolet and visible spectrophotometry

VM26:

Teniposide

VP16:

Etoposide

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Acknowledgments

CG Silva is grateful to Dr PM Dewick who first introduced her to the research on Podophyllum lignans and tissue culture of Berberidaceae species at the University of Nottingham (UK). PRV Campana is grateful to FAPEMIG for the fellowship (BIP-00224-15). VL Almeida is grateful to CNPq for the fellowship (249299/2013-5). The authors are grateful to AWA Linghorn for revising the manuscript.

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Correspondence to Cláudia Gontijo Silva , Vera Lúcia de Almeida , Priscilla Rodrigues Valadares Campana or Marina Pereira Rocha .

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Silva, C.G., de Almeida, V.L., Campana, P.R.V., Rocha, M.P. (2016). Plant Cell Cultures as Producers of Secondary Metabolites: Podophyllum Lignans as a Model. In: Jha, S. (eds) Transgenesis and Secondary Metabolism. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-27490-4_3-1

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