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E-Postaahmet.dogan@mersin.edu.tr
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ÜnvanArş.Gör.
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YÖK Araştırmacı No375011
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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
Doğan, Ahmet
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 co...
Antiproliferative effects of hazelnut cell culture extract on the different cancer cell lines
Doğan, Ahmet
The increasing incidence of cancer has necessitated the discovery of novel anticancer compound sources. The presence of taxanes in hazelnut cell cultures has promoted new promising pharmacotherapeutic applications. The antiproliferative properties of hazelnut (Corylus avellana cv. 'Kalınkara') cell culture extracts against different human cancer cell lines (HeLa, MCF-7, MDA-MB-231, A549) with Beas-2B as control were evaluated. The cytotoxicity of C. avellana culture extract (5 µM, 10 µM, and 20 µM) on all cell lines was evaluated with xCELLigence Real Time Cell Analysis System. Mitotic activity (450-655 nm), BrdU activity (450-550 nm) and caspase 3,7 activity (490-520 nm) were analyzed with a spectrophotometer through 24, 48, and 72 hours. Based on the values obtained from the xCELLigence Cell Analysis System, a 10 µM concentration of the culture extract was assigned as the IC50 dose. Culture extracts at 10 µM enhanced the reduction in the proliferation of all cancer cells assayed. The highest decrease in mitotic (59.32%) and BrdU (53.77%) activity was observed in A549 lung cancer cells. However, caspase 3,7 activity (35.08%) was the highest in aggressive MDA-MB-231 breast cancer cells. The culture extracts decreased the viability of A549 cells to a greater extent than ...
Aquatic toxic effect of epoxide derivatives on model organism Dapnia magna
Doğan, Ahmet | Özdemir, Birgül | Şimşek Kuş, Nermin
Since epoxides, which are found as natural products, show a wide range of biological activities, scientists have always been interested in studies on this subject. There are epoxides with very different substituents in the literature. For example, epoxides with lactone as paniculide A, amino as anticapsin, hydroxide as Eutypoxide B and Eutypoxide C are used as drugs by showing biological activity. Based on the studies in the literature, we planned to study the biological activity of molecules that do not contain amino, lactone and hydroxyl groups. For this purpose, we first performed the Diels-Alder reaction of 2,3-dimethyl-1,3-butadiene (1) with benzoquinone (2), in the next step, epoxidation reaction was targeted. Our research group previously showed that epoxide derivatives with anticancer properties effectively decrease cell viability of the ovarian cancer line (SKOV) and suppress cell migration of the line. Drugs are metabolized by the body and their metabolic residues are eliminated to aquatic systems. Therefore, it has become important to investigate the aquatic toxicity of drugs. Daphnia toxicity test is widely applied in aquatic toxicity studies. In this study, the chronic toxicity in water of the epoxide derivative 4 with six different concentration (2 nM, 5...
Fındık (Corylus avellana L.) hücre kültürlerinde metabolizma mühendisliği yaklaşımı ile taksan biyosentezinin uyarılması
Doğan, Ahmet
Paklitaksel akciğer, yumurtalık ve meme kanserinin yanı sıra Kaposi sarkomunun tedavisinde yaygın olarak kullanılan bir diterpenoiddir. Fındık (Corylus avellana L.) hücre süspansiyon kültürleri, paklitakselin yanı sıra 10-deasetil bakkatin III, bakkatin III ve sefalomannin gibi önemli taksanların üretimi için uygun sistemlerdir. Bununla birlikte, C. avellana hücre süspansiyon kültürlerinde üretiminin taksanların artırılması için çeşitli elisitörlerin kullanılması gerekmiştir. Bu tez çalışması kapsamında taksan üretimini artırmaya yönelik elisitasyon uygulaması için antikanser taksanları içeren bir Türk fındık çeşidi olan Corylus avellana cv. Kalınkara'da aktif bölünen kalluslar elde edilmiş ve bu kalluslardan hücre süspansiyon kültürleri kurulmuştur. Altı aylık homojenize hücre süspansiyon kültürlerine, logaritmik evrenin ortasına karşılık gelen kültürlemenin 17. gününde yapılan 1 µM koronatin elisitörü, 3 µM fenilalanin öncülü ve 50 mM metil-β-siklodekstrin nano-taşıyıcısının ayrı ayrı ve kombinasyon halindeki uygulamaların etkileri kültürlerin üreme özellikleri (biyokütle birikimi ve hücre canlılığı) ile taksan metabolitlerinin üretimi arasındaki ilişkinin anlaşılması için incelenmiştir. C. avellana Kalınkara hücre süspansiyon kültürlerinde koronatin, fenilalanin ve korona...
Enhancement of taxane production in cell suspension culture of Corylus avellana L. Kalınkara by elicitation and precursor feeding
Doğan, Ahmet
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 pac...
Türk Fındık Çeşitlerinde Antikanser Taksanların Biyoteknolojik Üretimi için Optimize Edilmiş Model Hücre Kültür Sistemi
Doğan, Ahmet
Paklitaksel çeşitli kanser hastalıklarının tedavisinde yaygın olarak kullanılan bir diterpenoiddir. Fındık (Corylus avellana L.) hücre süspansiyon kültürleri, paklitakselin (PTX) yanı sıra, çeşitli kanserlerde etkinliği yakın zamanda gösterilen sefalomannin (CEPH) ve bu taksanların yarı sentezinde kullanılan öncüller olan 10-deasetil bakkatin III (10DAB) ve bakkatin III (BACIII) gibi önemli taksanların üretimi için uygun sistemlerdir. Biyoteknolojik yolla taksan üretimi için antikanser sekonder metabolitlerin üretiminin artırılması gerekmektedir. Türk fındık çeşitlerinden Kalınkara hücre süspansiyon kültürlerinde biyokütlenin ve hücre dışına salgılanan taksanların üretiminin artırılması için elisitasyon koşulları ilk kez belirlenmiştir.