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<p>Taxanes are effective, natural-derived medicines widely utilized against various cancer types. Hazelnut (<i>Corylus avellana</i> L.) cell suspension culture systems offer a promising alternative platform for taxane production. The intracellular yields of taxanes in hazelnut cells can be elevated through elicitors such as coronatine. However, coronatine exhibits toxic effects on cell viability. Recently, methyl-β-cyclodextrins have been used to facilitate the secretion of taxanes into the extracellular medium, thereby preserving culture biomass. Herein, this study investigated for the first time the effects of 1&#xa0;µM coronatine, alone or in combination with 50&#xa0;mM methyl-β- cyclodextrin, on biomass accumulation and taxane production in cell suspension cultures of the Turkish hazelnut Kalınkara cultivar, which determined taxane profile and responds positively to elicitation. The results demonstrated that coronatine treatment increased intracellular paclitaxel content (32.008&#xa0;µg/mL) by 1.9-fold than control although it reduced the growth (1.28-fold) and viability (1.05-fold) of the suspended cells compared to the control. Methyl-β-cyclodextrin facilitated the extracellular export of paclitaxel (2.667&#xa0;µg/mL) without compromising cell growth whereas no paclitaxel secretion was observed under control conditions. When methyl-β-cyclodextrin was treated together with coronatine, the detrimental effects of coronatine on cell growth (1.18-fold) and viability (1.03-fold) were mitigated. Moreover, this dual treatment showed a synergistic effect, enhancing the extracellular yield of taxanes by 8.85-fold compared to the control, particularly cephalomannine (6.017&#xa0;µg/mL, 11.5-fold) and paclitaxel (2.771&#xa0;µg/mL). The addition of coronatine and methyl-β-cyclodextrin to <i>C. avellana</i> cv. Kalınkara cultivar cell cultures is therefore an attractive strategy to yield extracellular taxane accumulation, and may applied to other hazelnut cultivars.</p>

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Synergistic effects of methyl-β-cyclodextrin and coronatine on biomass accumulation and taxane secretion in Corylus avellana L. cell suspension cultures

  • 期刊论文

  • 发表日期：

    2025年9月17日

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  • Ahmet Dogan,
  • Sule Ari

摘要

Taxanes are effective, natural-derived medicines widely utilized against various cancer types. Hazelnut (Corylus avellana L.) cell suspension culture systems offer a promising alternative platform for taxane production. The intracellular yields of taxanes in hazelnut cells can be elevated through elicitors such as coronatine. However, coronatine exhibits toxic effects on cell viability. Recently, methyl-β-cyclodextrins have been used to facilitate the secretion of taxanes into the extracellular medium, thereby preserving culture biomass. Herein, this study investigated for the first time the effects of 1 µM coronatine, alone or in combination with 50 mM methyl-β- cyclodextrin, on biomass accumulation and taxane production in cell suspension cultures of the Turkish hazelnut Kalınkara cultivar, which determined taxane profile and responds positively to elicitation. The results demonstrated that coronatine treatment increased intracellular paclitaxel content (32.008 µg/mL) by 1.9-fold than control although it reduced the growth (1.28-fold) and viability (1.05-fold) of the suspended cells compared to the control. Methyl-β-cyclodextrin facilitated the extracellular export of paclitaxel (2.667 µg/mL) without compromising cell growth whereas no paclitaxel secretion was observed under control conditions. When methyl-β-cyclodextrin was treated together with coronatine, the detrimental effects of coronatine on cell growth (1.18-fold) and viability (1.03-fold) were mitigated. Moreover, this dual treatment showed a synergistic effect, enhancing the extracellular yield of taxanes by 8.85-fold compared to the control, particularly cephalomannine (6.017 µg/mL, 11.5-fold) and paclitaxel (2.771 µg/mL). The addition of coronatine and methyl-β-cyclodextrin to C. avellana cv. Kalınkara cultivar cell cultures is therefore an attractive strategy to yield extracellular taxane accumulation, and may applied to other hazelnut cultivars.