Gümüş nanopartiküllerle etkileşen berberin, honokiol ve SirReal2 moleküllerininin anti-kanser özelliklerinin kanser hücre hatlarında araştırılması
Investigation of anticancer properties of berberine, honokiol and SirReal2 molecules interacting with silver nanoparticles in cancer cell lines
Yazar: MERYEM İÇEN
Danışman: DOÇ. DR. ÖZKAN ÖZDEN
Kafkas Üniversitesi / Fen Bilimleri Enstitüsü / Biyomühendislik Ana Bilim Dalı
Derece: Yüksek Lisans, 2022
Konu: Biyoloji = Biology ; Biyomühendislik = Bioengineering ; Biyoteknoloji = Biotechnology
Dizin: Berberin = Berberine ; Gümüş nanopartiküller = Silver nanoparticles ; Nanopartiküller = Nanoparticles ; Neoplazmlar = Neoplasms ; Sirtuin = Sirtuin

Özet:
Kanser dünya genelinde insanların ölümüne neden olan hem fizyolojik hem de psikolojik olarak insanı olumsuz etkileyen hastalık grubu olarak görülmektedir. Bu hastalığa karşı çeşitli tedavi yöntemleri olmasına rağmen gösterdikleri yan etki, maliyet gibi faktörler tedavileri olumsuz etkilemektedir. Son zamanlarda nanopartiküller, yapıları ve sahip oldukları çeşitli özellikler sayesinde birbirinden farklı alanlarda olduğu gibi kanser çalışmalarında da görülmektedir. Metabolizma, üreme, oksidatif stres, kardiyovasküler, nörodejeneratif gibi fizyolojik olaylar ve yaşlanmaya bağlı olan hastalıklarda aktif rol oynayan sirtuin (SIRT) proteinlerinin de kanser tedavileri için önemli katkılar sağlayabildiği rapor edilmiştir. Bu çalışmada biyosentez yöntemi kullanılarak elde edilen düşük maliyetli, verimli, çevreye faydalı nanopartiküllerin çeşitli moleküllerle etkileştirilmesi sağlanılarak kolon ve meme kanserine karşı göstermiş olduğu etkileri incelemeyi potansiyel ilaç olabilme durumlarını araştırmayı amaçlamaktayız. Çevreci, düşük maliyetli olarak bilinen yeşil sentez yöntemiyle gümüş nanopartikül (AgNP) eldesi sağlanıldı. Elde edilen AgNP, Fourier dönüşümlü kızılötesi spektroskopisi
(FT-IR), ultraviyole-görünür bölge spektroskopi analizi (UV-vis), taramalı elektron

Abstract:
Cancer is seen as a group of diseases that cause the death of people around the world and negatively affect people both physiologically and psychologically. Although there are various treatment methods against this disease, factors such as side effects and cost affect the treatments negatively. Recently, nanoparticles have been seen in cancer studies as
well as in different fields, thanks to their structures and various properties. It has been reported that sirtuin (SIRT) proteins, which play an active role in diseases related to aging and physiological events such as metabolism, reproduction, oxidative stress, cardiovascular, neurodegenerative, can also make important contributions to cancer
treatments. In this study, we aim to investigate the effects of low-cost, efficient, environmentally beneficial nanoparticles obtained by using the biosynthesis method against colon and breast cancer by activating them with various molecules and to investigate their potential drug status. Silver nanoparticle (AgNP) was obtained by the green synthesis method known as environmentally friendly and low cost. The resulting AgNP was identified by characterization processes using Fourier transform infrared spectroscopy (FT-IR), visible spectroscopy analysis (UV-vis), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) methods. In this study, Honokiol and Berberine, which were used as drugs against various diseases in the past, and silver nanoparticles obtained with SirReal2 molecules known as SIRT inhibitors were activated, and repeated cell viability tests were performed against breast and colon cancer during 48 hours of application. Western blot analysis was performed and protein levels such as PARP, SIRT2, SIRT3, LDHA, PDH were checked. In addition, apoptosis levels were examined by acridine orange staining. According to our research, Berberine (100 µM) dose reduces the viability of MDA-MB-231 breast cancer cell line by ~74% (p<0.001). The AgNPactivated form of Berberine (BAgNP), on the other hand, was found to severely reduce cell survival by ~88% (p<0.001). In DLD-1 colon cancer cell, the AgNP-activated form of Honokiol (HAgNP) reduced the viability of the (25 µM) dose by ~18% (p<0.05). In the other colon cancer HCT-116 cell line, it is seen that Honokiol (25 µM) viability decreased by ~43% (p<0.001) and HAgNP (25 µM) decreased by ~71% (p<0.001), thus providing a significant effect on cell survival. and also these strong effects on cells were confirmed by cell morphologies. According to the DLD-1 protein expression findings, the amount of cleaved PARP protein increased when interacted with nanoparticles. AgNP-activated version of SirReal2 (SAgNP) increased the amount of PDH protein. There was an increase for SIRT3 proteins in the HAgNP and Berberine groups compared to the control. According to the protein expression findings of MDA-MB-231, there was an increase in cleaved
PARP protein in BAgNP compared to Berberine for cleaved PARP protein and in SAgNP according to SirReal2. According to the results we obtained, it was observed that the combination of Berberine, Honokiol and SirReal2 molecules with silver nanoparticles has significant anti-cancer properties against breast and colon cancers. From this point of view, the interaction of molecules with nanoparticles has revealed the idea that it can be a potential anti-cancer drug for colon and breast cancer.