Enhancement of taxane production in cell suspension culture of Corylus avellana L. Kalınkara by elicitation and precursor feeding

Abstract

Paclitaxel (trademark Taxol®) is the most effective chemotherapeutic agent against a wide range of cancers. Hazelnut (Corylus avellana L.) cell culture is a promising and inexpensive strategy for producing paclitaxel and related taxanes. This study evaluated the effect of elicitation and taxane precursor feeding for the enhancement of taxanes in a Turkish hazelnut (C. avellana cv. ‘Kalınkara’) cell suspension culture. Elicitor methyl jasmonate (100, 200 and 300 µmol L⁻¹) and precursor phenylalanine (3μmol, 3 and 6 mmol L⁻¹) were tested in cell suspension cultures. While methyl jasmonate increased the accumulation of taxanes, especially cephalomannine, via induction of the paclitaxel biosynthetic pathway, phenylalanine slightly induced the conversion of 10-deacetylbaccatin III and baccatin III to the end product paclitaxel (0.5349 µg g⁻¹). The results showed that 200 µmol L⁻¹ methyl jasmonate led to significantly greater induction of taxanes than 100 and 300 µmol L⁻¹. The amount of cephalomannine (331.6 µg g⁻¹) in cell suspension cultures elicited by 200 µmol L⁻¹ methyl jasmonate was 8-fold higher than that in the control (41.61 µg g⁻¹), while 10-deacetylbaccatin III (6.174 µg g⁻¹) and baccatin III (3.956 µg g⁻¹) increased almost twice as much as the control. The highest total paclitaxel yield was 5.453 µg g⁻¹ in the same culture conditions. In conclusion, cell culture systems of C. avellana L. cv. ‘Kalınkara’ hazelnut, established for the first time, may become a potential candidate for industrial-level production of cephalomannine and other taxanes with further optimization.

Keywords:

• Hazelnut
• anti-cancer
• taxanes
• cell suspension culture
• methyl jasmonate
• phenylalanine

Acknowledgments

The authors would like to thank Dr. Umit SERDAR (Ondokuz Mayıs University, Ordu, Turkey) for providing hazelnut seeds. The authors are also thankful to Istanbul University Bioanalytical Research Laboratory.

Author contributions

SA designed the study, acquired the funding and wrote the manuscript with the contributions of AD and IGA; IGA performed experiments; AD analyzed data. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data supporting this study’s findings are available from the corresponding author (SA), upon reasonable request.

Additional information

Funding

This work was supported by the Research Fund of Istanbul University under a Grant No. FYL-2019-29216.