Farklı kanser modellerinde izopropilketominin'in anti-kanser etkisinin değerlendirmesi
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kanser, ölümcül hastalıkların başını çekmektedir. Tedavi seçeneklerinin yeterli olmaması, gelişen ilaç direnci ve hastalığın tekrarlanabilir olmasından dolayı, geliştirilecek yeni tedavi yöntemlerine ve yan etkisi olmayan düşük dozlarda aktivite gösteren doğal kaynaklı ilaç etken maddelerine olan ihtiyaç giderek artmaktadır. Günümüzde denizel habitatlarda yaşayan canlılar ilaç etken maddelerinin eldesi açısından sıklıkla değerlendirilen kaynaklardan biridir. Denizel canlılar açısından ise son yıllarda sünger ilişkili funguslar dikkat çekmektedir. Genom büyüklüğünün bakterilere göre daha fazla olması da sünger ilişkili fungusları verimli doğal ürün kaynakları haline getirmektedir. Önerilen projede, Türkiye kıyılarından toplanan Agelas oroides sünger türünden izole edilen Aspergillus carneus fungal suşundan izole edilen Kinazolinon türevi olan İzopropilketominin molekülünün farklı kanser türlerinin tedavisinde kullanılabilme potansiyelinin belirlenmesi amaçlanmaktadır. Bunun için mikrobiyolojik yöntemlerle üretimi yapılmış ve ,Aspergillus carneus suşunun fermentasyon sürecinde sentezlenerek kromatografik yöntemlerle izole edilmiş olan İzopropilketominin metabolitinin in vitro denemelerle pankreas, beyin, prostat, kanser hücrelerine karşı sitotoksik özellikleri MTT testi ile incelenerek kanser tedavilerinde kullanılma potansiyeli araştırılacaktır. Etken maddenin apoptozun moleküler mekanizması üzerindeki etkileri Annexin V yöntemi ile değerlendirilecektir. Etken maddenin hücre döngüsü progresyonu üzerindeki etkisi "Cycle Test Plus DNA Reagent" kit ile incelenecektir. Son olarak etken maddenin kanser progresyonunda multifonskiyonel role sahip olan Wnt sinyal yolağı üzerindeki etkisinin ortaya çıkarılması için sinyalizasyonda görevli proteinleri kodlayan genlerin transkriptom düzeyde incelenmesi ile nihayet kazanacaktır. Projenin sonunda, İzopropilketominin molekülünün sitotoksik özellikleri belirlenerek, yeni kanser tedavisi geliştirilmesindeki potansiyeli değerlendirilecektir. Ardından aktivite gösterdiği kanser türleri üzerine İzopropilketominin molekülünün, organoid ve in vivo çalışmalar ile potansiyelinin desteklenmesi amaçlanmaktadır.
Cancer is one of the most deadly diseases. Due to inadequate treatment options, evolving drug resistance, and the reproducibility of the disease, there is an increasing need for new treatments and naturally derived agents that are effective at low doses without side effects. Nowadays, organisms that live in marine habitats are one of the sources that are often studied in terms of obtaining pharmaceutical agents. Marine organisms, including fungi related to sponges, have recently attracted much attention. The fact that their genome is larger than that of bacteria makes sponge-associated fungi, efficient sources of natural products. The proposed project aims to determine the potential of using the İso-propylchaetominin molecule, a quinazolinone derivative isolated from the fungal strain Aspergillus carneus, derived from the sponge species Agelas oroides from the Turkish coast, for the treatment of various cancers. To this end, the cytotoxic properties of İso-propylchaetominin metabolite produced by microbiological methods and synthesized during the fermentation process of Aspergillus carneus strain and isolated by chromatographic methods are investigated by MTT assay, and its potential for use in cancer treatment is studied by in vitro experiments. The effects of the drug on the molecular mechanism of apoptosis are evaluated by the Annexin-V method. The impact of the drug on cell cycle progression will be investigated using the Cycle Test Plus DNA Reagent kit. Finally, to uncover the effect of the active substance on the Wnt signaling pathway, which plays a multifunctional role in cancer progression, the genes encoding the proteins involved in signaling will be studied at the transcriptome level. At the end of the project, the cytotoxic properties of the İso-propylchaetominin molecule will be determined, and its potential for the development of new cancer treatments will be evaluated. Subsequently, the potential of the İso-propylchaetominin molecule in cancers in which it shows activity will be supported by organoid and in vivo studies.
Cancer is one of the most deadly diseases. Due to inadequate treatment options, evolving drug resistance, and the reproducibility of the disease, there is an increasing need for new treatments and naturally derived agents that are effective at low doses without side effects. Nowadays, organisms that live in marine habitats are one of the sources that are often studied in terms of obtaining pharmaceutical agents. Marine organisms, including fungi related to sponges, have recently attracted much attention. The fact that their genome is larger than that of bacteria makes sponge-associated fungi, efficient sources of natural products. The proposed project aims to determine the potential of using the İso-propylchaetominin molecule, a quinazolinone derivative isolated from the fungal strain Aspergillus carneus, derived from the sponge species Agelas oroides from the Turkish coast, for the treatment of various cancers. To this end, the cytotoxic properties of İso-propylchaetominin metabolite produced by microbiological methods and synthesized during the fermentation process of Aspergillus carneus strain and isolated by chromatographic methods are investigated by MTT assay, and its potential for use in cancer treatment is studied by in vitro experiments. The effects of the drug on the molecular mechanism of apoptosis are evaluated by the Annexin-V method. The impact of the drug on cell cycle progression will be investigated using the Cycle Test Plus DNA Reagent kit. Finally, to uncover the effect of the active substance on the Wnt signaling pathway, which plays a multifunctional role in cancer progression, the genes encoding the proteins involved in signaling will be studied at the transcriptome level. At the end of the project, the cytotoxic properties of the İso-propylchaetominin molecule will be determined, and its potential for the development of new cancer treatments will be evaluated. Subsequently, the potential of the İso-propylchaetominin molecule in cancers in which it shows activity will be supported by organoid and in vivo studies.
Açıklama
Anahtar Kelimeler
Tıbbi Biyoloji, Medical Biology
