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    Apoptosis-inducing, anti-angiogenic and anti-migratory effects of a dinuclear Pd(II) complex on breast cancer: A promising novel compound
    (Academic Press Inc Elsevier Science, 2024) Genel, Merve Erkisa; Adacan, Kaan; Selvi, Selin; Kutucu, Deniz Erol; Uvez, Ayca; Armutak, Elif Ilkay; Sengul, Abdurrahman
    Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer.
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    Highly promising antitumor agent of a novel Platinum(II) complex bearing a tetradentate chelating ligand
    (Amer Chemical Soc, 2020) Yılmaz, İsmail; Akar, Remzi Okan; Erkısa Genel, Merve; Selvi, Selin; Şengül, Abdurrahman; Ulukaya, Engin
    A new mononuclear cationic platinum(II) coordination compound with 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine (L) ligand having N-4-tetradentate binding pocket [Pt(L)]-Cl-2.2H(2)O (Complex 1) was synthesized and characterized by FTIR(ATR), UV-vis, H-1 NMR, APCI and MALDI MS, and CHN analysis. The antigrowth effect of Complex 1 was tested in breast cancer (MDA-MB-231), lung cancer (A549), colorectal cancer (HCT-116), prostate cancer (PC-3) cell lines, and bronchial epithelial cell line (BEAS-2B) by the SRB and ATP cell viability assays. Apoptosis was detected with Annexin V, mitopotential, BCL-2 inactivation, and gamma H2AX assays by flow cytometry. Complex 1 was found to have cytotoxic activity of MDA-MB-231, A549, HCT-116, and PC-3 cancer cell lines in a dose-dependent manner for 48 h. Complex 1 has been found to cause cell death through different mechanisms depending on the type of cancer. The findings indicated that complex induced intrinsic apoptosis with the increased mitochondrial membrane depolarization level, Bcl-2 inactivation, and DNA damage in PC-3 and A549 cell lines.
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    Key actors in cancer therapy: epigenetic modifiers
    (Tubitak Scientific & Technical Research Council Turkey, 2019) Akar, Remzi Okan; Selvi, Selin; Ulukaya, Engin; Aztopal, Nazlıhan
    Epigenetic reprogramming plays a crucial role in the tumorigenicity and maintenance of tumor-specific gene expression that especially occurs through DNA methylation and/or histone modifications. It has well-defined mechanisms. It is known that alterations in the DNA methylation pattern and/or the loss of specific histone acetylation/methylation markers are related to several hallmarks of cancer, such as drug resistance, sternness, epithelial-mesenchymal transition, and metastasis. It has also recently been highlighted that epigenetic alterations are critical for the regulation of the stemlike properties of cancer cells (tumor-initiating cells; cancer stem cells). Cancer stem cells are thought to be responsible for the recurrence of cancer which makes the patient return to the clinic with metastatic tumor tissue. Hence, the dysregulation of epigenetic machinery represents potential new therapeutic targets. Therefore, compounds with epigenetic activities have become crucial for developing new therapy regimens (e.g., antimetastatic agents) in the fight against cancer. Here, we review the epigenetic modifiers that have already been used in the clinic and/or in clinical trials, related preclinical studies in cancer therapy, and the smart combination strategies that target cancer stem cells along with the other cancer cells. The emerging role of epitranscriptome (RNA epigenetic) in cancer therapy has also been included in this review as a new avenue and potential target for the better management of cancer-beneficial epigenetic machinery.
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    Potent bir anti-kanser bileşik: terpiridin içeren dinükleer palladyum(II) kompleksinin {[pd(sac)(terpy)](sac)} [pd2(terpy)2(m? tas? n1,n4)]so4?11h2o meme kanseri hücreleri üzerindeki sitotoksik/sitostatik etkilerinin ve mekanizmalarının araştırılması
    (İstinye Üniversitesi / Sağlık Bilimleri Enstitüsü, 2019) Selvi, Selin
    Meme kanseri, tüm dünyada morbidite ve mortalite açısından önde gelen kanser türlerinden biridir. Tüm dünyada kadınlar arasında en sık görülen kanser tipi olup, tüm kanser ölümleri arasında ikinci sırada yer almaktadır. Meme kanseri tedavisinde cerrahi girişim ve radyoterapinin yanı sıra kemoterapi de önemli bir yer tutmaktadır. Platin/Palladyum bazlı koordinasyon bileşikleri 25 yıldan uzun süredir kemoterapi tedavisinde kullanılmaktadır. Yapılan çalışmalar, sisplatinin birçok kanser türünde güçlü bir anti-tümör aktiviteye sahip olduğunu göstermiştir. Fakat sisplatinin aşırı toksik olması, nefrotoksisiteye (böbrek hasarı) ve ototoksisiteye (yüksek işitme kaybı) neden olmaktadır. Bu nedenle sisplatinden farklı özelliklere sahip, daha etkili olabilecek yeni kompleksler sentezlenmekte ve anti-kanser aktiviteleri araştırılmaktadır. Bu amaçla sentezlenen bileşiklerden biri de çok çekirdekli metal kompleksleridir. Özellikle DNA?ya bağlanma afinitelerinin yüksek olması ve kanser hücreleri üzerinde güçlü sitotoksik etki göstermesi, bu kompleksleri daha etkili tedavi yaklaşımlarını ortaya çıkarılması açısından önemli hale getirmiştir. Sunulan tezde, dinükleer Pd(II) kompleksinin, meme kanseri hücrelerini hedefleyerek güçlü bir sitotoksik ve sitostatik aktiviteye neden olduğu bulunmuş olup bulgular yeni bir tedavi seçeneği olarak umut vermektedir. Sonuç olarak, Dinükleer, Palladyum tedavisinin, kadın meme kanseri tedavisinde kullanılabileceği öngörülerek in vivo deneylerin yapılması gerekmektedir