In vitro cell cultures obtained from different explants of Corylus avellana produce Taxol and taxanes.
BACKGROUND
Taxol is an effective antineoplastic agent, originally extracted from the bark of Taxus brevifolia with a low yield. Many attempts have been made to produce Taxol by chemical synthesis, semi-synthesis and plant tissue cultures. However, to date, the availability of this compound is not sufficient to satisfy the commercial requirements. The aim of the present work was to produce suspension cell cultures from plants not belonging to Taxus genus and to verify whether they produced Taxol and taxanes. For this purpose different explants of hazel (Corylus avellana species) were used to optimize the protocol for inducing in vitro callus, an undifferentiated tissue from which suspension cell cultures were established.


RESULTS
Calli were successfully induced from stems, leaves and seeds grown in various hormone concentrations and combinations. The most suitable callus to establish suspension cell cultures was obtained from seeds. Media recovered from suspension cell cultures contained taxanes, and showed antiproliferative activity on human tumour cells. Taxol, 10-deacetyltaxol and 10-deacetylbaccatin III were the main taxanes identified. The level of Taxol recovered from the media of hazel cultures was similar to that found in yew cultures. Moreover, the production of taxanes in hazel cell cultures increased when elicitors were used.


CONCLUSIONS
Here we show that hazel cell cultures produce Taxol and taxanes under controlled conditions. This result suggests that hazel possesses the enzymes for Taxol production, which until now was considered to be a pathway particular to Taxus genus. The main benefit of producing taxanes through hazel cell cultures is that hazel is widely available, grows at a much faster rate in vivo, and is easier to cultivate in vitro than yew. In addition, the production of callus directly from hazel seeds shortens the culture time and minimizes the probability of contamination. Therefore, hazel could become a commercial source of Taxol and taxanes, both to be used as new therapeutic agents or as new precursors for Taxol semi-synthesis.
Bestoso
Federica
F
Laboratory of Plant and Pharmaceutical Biotechnology, Advanced Biotechnology Center (ABC), Largo R. Benzi, 10, 16132 Genova, Italy. federicabestoso@libero.it <federicabestoso@libero.it>
Ottaggio
Laura
L
Armirotti
Andrea
A
Balbi
Alessandro
A
Damonte
Gianluca
G
Degan
Paolo
P
Mazzei
Mauro
M
Cavalli
Francesca
F
Ledda
Bernardetta
B
Miele
Mariangela
M
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D031211:Corylus / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage* / Q000302:isolation & purification / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D043823:Taxoids; D017239:Paclitaxel