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    In silico and in vitro evaluation of oxypeucedanin-induced anticancer activity: Mitotoxicity?
    (2023) Ergüç, Ali; Okur, Hayati; Karakuş, Fuat; Albayrak, Gökay; Arzuk, Ege; Baykan, Şüra
    Aim: This study aims to evaluate the alterations in Oxypeucedanin (OXY)-mediated anticancer activity in different media. Second aim is to predict the affinity of OXY to electron transfer chain (ETC) complexes. Materials and Methods: MTT and LDH leakage assays were performed with OXY. Molecular docking studies were also conducted to predict the affinity of OXY to ETC complexes. Results: 250 µM OXY reduced viability in glucose media. ≥50 µM OXY decreased viability in galactose media. ≥50 µM OXY increased membrane disruption in galactose media. Molecular docking studies also showed that OXY might possess the capacity to bind to the inhibition sites of Complex I and IV. Conclusion: Galactose-conditioned media exacerbated the OXY-mediated cytotoxicity. Preliminary results suggested that mitotoxicity might take part in anticancer activity. Furthermore, OXY might cause ETC dysfunctions due to selective inhibition of Complex I and IV.
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    Öğe
    Isoimperatorin-mediated anticancer activity: Role of mitochondrial dysfunction in hepg2 cells
    (Ankara Üniversitesi Eczacılık Fakültesi, 2023) Ergüç, Ali; Arzuk, Ege; Albayrak, Gökay; Karakuş, Fuat; Okur, Hayati; Baykan, Şüra
    Objective: The first goal of the present study is to investigate the role of mitochondria due to the Crabtree effect in HepG2 cells exposed to ISO in either glucose- or galactose-conditioned media. The second aim is to predict the interactions between electron transport chain (ETC) complexes and ISO, which might be the possible reason for mitochondrial dysfunction. Material and Method: Cell viability and membrane damage for HepG2 cells exposed to ISO (12.5, 25, 50, 100, and 250 µM) were assessed by MTT and LDH leakage assays in either glucose- or galactose-conditioned media. The affinity of ISO to ETC complexes was also determined by a molecular docking study. Result and Discussion: MTT assay showed that 250 µM ISO leads to cytotoxic activity in glucoseconditioned media, while 25 µM and higher concentrations of ISO decrease cell viability in galactose-conditioned media. A membrane damage assay conducted in a glucose-conditioned media assay revealed that 250 µM ISO disrupts the cell membrane. 100 and 250 µM ISO increased membrane damage in galactose-conditioned media. According to docking simulations, binding affinities of ISO to ETC complexes are in descending order: Complex IV > Complex I > Complex III > Complex II. Inhibition of complex IV by ISO inhibits the transfer of electrons from cytochrome c to oxygen, and the proton gradient collapses. The present study proposed that ISO leads to mitochondrial dysfunction via inhibition of the ETC.
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    Öğe
    Matairesinol induced antiproliferative effects via mitochondrial dysfunction in HepG2 cells
    (Marmara Univ, Fac Pharmacy, 2024) Arzuk, Ege; Erguc, Ali; Demir, Serhat; Unver Somer, Nehir; Tan, Iclal; Atis, Ecrin
    Hepatocellular carcinoma is one of the most severe and life-threatening types of cancer. The conventional treatment of hepatoma has significant challenges due to the adverse effects of chemotherapy, leading to treatment failure and decreased survival. Therefore, developing and investigating novel and safer anticancer drugs and establishing more effective therapeutic regimens is a crucial field of research. The Haplophyllum megalanthum-derived compound matairesinol has demonstrated antiproliferative and antitumor activity against various types of cancer, including pancreatic, breast, and prostate cancer. However, the potential effects of matairesinol on liver cancer, as well as the underlying molecular mechanisms associated with its anticancer activity, have yet to be thoroughly elucidated. In the current study, we demonstrated that matairesinol inhibited the viability of human hepatoma cells in a dose-dependent manner. Besides, at IC50 and higher doses, matairesinol induced oxidative stress and impaired mitochondrial membrane potential and ATP levels, two evidence of mitochondrial damage. Moreover, matairesinol exposure led to significant caspase-3 activation, a hallmark of apoptosis. These results indicate that mitochondrial damage and caspase-3 activation may contribute to the cytotoxic effect of matairesinol on liver cancer cells.
  • [ X ]
    Öğe
    Oksipösedanin kaynaklı antikanser aktivitenin in siliko ve in vitro değerlendirilmesi: Mitotoksisite?
    (Adıyaman Üniversitesi, 2023) Ergüç, Ali; Okur, Hayati; Karakuş, Fuat; Albayrak, Gökay; Arzuk, Ege; Baykan, Şüra
    Amaç: Çalışmanın amacı, farklı ortamlarda Oksipösedanin (OKS) aracılı antikanser aktivitedeki değişiklikleri değerlendirmektir. İkinci amaç, OKS’inin elektron transfer zincirine (ETZ) karşı afinitesini öngörmektir. Gereç ve Yöntem: MTT ve LDH sızma deneyleri OKS ile gerçekleştirilmiştir. Ayrıca, OKS’inin ETZ komplekslerine karşı afinitesini öngörmek için moleküler kenetlenme çalışmaları uygulanmıştır. Bulgular: Glukoz içeren ortamda 250 µM OKS canlılığı azaltmıştır. Galaktoz içeren ortamda ?50 µM OKS hücre canlılığını azalmıştır. Galaktoz içeren ortamda ?50 µM OKS membran parçalanmasını artırmıştır. Moleküler kenetlenme çalışmaları, OKS'inin Kompleks I ve IV'ün inhibisyon bölgelerine bağlanma kapasitesine sahip olabileceğini göstermektedir. Sonuç: Galaktoz içeren ortam, OKS aracılı sitotoksisiteyi artırmıştır. Ön sonuçlar, antikanser aktivitede mitotoksisitenin yer alabileceğini göstermektedir. Ayrıca OKS, Kompleks I ve IV'ün seçici inhibisyonu nedeni ile ETZ disfonksiyonuna neden olabilmektedir.