Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans.

Sullivan Renouard,Benoit Maunit,François Mesnard,Samantha Drouet,Christophe Hano,Eric Lainé,Barbara Medvedec,Nathalie Jullian,Bilal Abbasi,Eric Gontier,Cyril Colas,Randolph Arroo,Joël Doussot,Cyrielle Corbin,Avninder Bhambra,Michèle Boitel

doi:10.3390/ijms19040990

Abstract

Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands.

Highlights

Podophyllotoxin (PPT; Figure 1) is a well-known aryltetralin lignan (ATL), which serves as a unique starting compound for the semi-synthesis of leading anticancer drugs [1]
We report on the establishment of fourteen hairy root (HR) lines as well as their physiological, molecular and biochemical characterizations leading to the selection of a productive L. flavum HR line
After 4 weeks of cultivation individual lines were isolated from different individual explants, denoted as HRLF15.1 to HRLF15.18, for lines initiated by A. rhizogenes strain ATCC 15834, and HRLF94.1 to HRLF94.16, for that initiated by the LBA 9402 strain

Summary

Introduction

Podophyllotoxin (PPT; Figure 1) is a well-known aryltetralin lignan (ATL), which serves as a unique starting compound for the semi-synthesis of leading anticancer drugs [1]. These drugs, including etoposide, teniposide and etopophos, are known to inhibit topoisomerase II and are widely used to treat several types of cancers [2,3]. PPT is known to inhibit the Herpes simplex type I virus replication [4] and some of its semi-synthetic derivatives possess pronounced anti-HIV properties [5]. The PPT-supply issue triggered an active search for alternative natural sources [7]

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Results

Conclusion