Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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Publisher: search.filters.publisher.ElsevierSubject: search.filters.subject.Apoptosis

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  • Article
    Design, Synthesis, and Evaluation of Anticancer Activities of 1,2-Diborolane Derivatives for Hepatocellular Carcinoma: an in Vitro and in Silico Study
    (Elsevier, 2026) Sahin, Yuksel; Antika, Gizem; Aktan, Cagdas; Metin, Kubilay; Ozgener, Huseyin
    Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and remains a major global health challenge due to limited treatment options and poor prognosis. Boron-containing compounds have garnered attention for their diverse biological activities, including pro-apoptotic effects in various types of cancer. In this study, we synthesized a panel of novel 1,2-N-substituted-1,2-diborolane derivatives and evaluated their antiproliferative, antimigratory, and apoptotic effects on hepatocellular carcinoma cell lines, HepG2 and Hep3B. Spectroscopic analyses confirmed the structural integrity of the synthesized compounds, revealing characteristic 1H-, 11B-, and 13C-NMR shifts consistent with boron-oxygen and boron-nitrogen bonding patterns. The derivatives, particularly compounds 2, 3, and 6, demonstrated potent and selective cytotoxicity toward HCC cells, with compound 3 exhibiting the lowest IC50 value (6.75 mu M) in HepG2 cells. Their time-dependent anti-proliferative effects were further supported by colony formation assays demonstrating long-term growth suppression, while wound healing assays revealed marked inhibition of HepG2 cell migration, indicating the compound's anti-metastatic potential. Our results demonstrate that the compound significantly induces apoptosis, modulates the expression of key apoptotic genes (Bax, Bcl-2, and caspase-3). In silico molecular docking further confirmed strong binding affinity to the anti-apoptotic Bcl-2 protein, supporting the proposed mechanism of action. These findings highlight the compound as a promising candidate for further preclinical evaluation in liver cancer therapy.
  • Article
    Citation - WoS: 4
    Citation - Scopus: 6
    Effect of Boramidic Acid Modified Carbon Nanotubes on Neurological, Morphological and Physiological Responses of Zebrafish (danio Rerio) Embryos and Larvae
    (Elsevier, 2024) Yigit, Aybek; Kokturk, Mine Ko; Yildirim, Serkan; Nazli, Dilek; Kiliccioglu, Metin; Sahin, Ayse; Alak, Gonca
    This study aimed to determine the potential toxicological effects of carbon nanotubes (CNTs), their modifications with ethylenediamine (ED) and boric acid (BA) on aquatic organisms. Specifically, the research focused on the morphological, physiological, and histopathological-immuno-histochemical responses in zebrafish (Danio rerio) embryos and larvae, via applying different concentrations of CNTs, CNT-ED, and CNT-ED-BA (Control, 5, 10, and 20 mg/L). The results indicated that 20 mg/L CNT nanoparticles were toxic to zebrafish larvae, with mortality rates increasing with CNT and CNT-ED concentrations, reaching 36.7 % at the highest CNT concentration. The highest dose caused considerable degeneration, necrosis, DNA damage, and apoptosis, as evidenced by histopathological and immunohistochemical tests. In contrast, despite their high concentration, CNT-ED-BA nanoparticles exhibited low toxicity. Behavioral studies revealed that CNT and CNT-ED nanoparticles had a more significant impact on sensory-motor functions compared to CNT-ED-BA nanoparticles. These findings suggest that modifying the nanosurface with boric acid, resulting in boramidic acid, can reduce the toxicity induced by CNT and CNT ED
  • Article
    Citation - WoS: 6
    Citation - Scopus: 7
    A Comprehensive Study on Doxorubicin-Loaded Aspartic Acid-Coated Magnetic Fe<sub>3</Sub>o<sub>4< Nanoparticles: Synthesis, Characterization and in Vitro Anticancer Investigations
    (Elsevier, 2024) Jafari, Nahideh; Mohammadpourfard, Mousa; Hamishehkar, Hamed
    Magnetic Fe3O4 nanoparticles (MNPs) hold significant potential across various scientific fields due to their notable properties. For biomedical applications, MNPs must be biocompatible, stable, and possess high magnetic potential. Aspartic acid (ASP) as a coating agent not only provides biocompatibility, stability, and high magnetic potential but also offers the potential for absorbing various drugs for targeted delivery due to its carboxyl and amino functional groups. So, in this study, we synthesized ASP-coated MNPs (ASP-MNPs) through a one-step co-precipitation method and loaded doxorubicin (DOX) onto these nanoparticles to create DOX-ASP-MNPs for targeted drug delivery. Characterization of the nanoparticle confirmed the crystal structure, spherical morphology, and improved size distribution of ASP-MNPs (8.53 +/- 2.56 nm) compared to uncoated MNPs (7.05 +/- 1.89 nm), as analyzed by XRD, FESEM, and TEM. FT-IR and zeta potential assessments (ZP = -6.3 mV for MNPs, ZP = -31.1 mV for ASP-MNPs) verified successful ASP binding, DOX loading, and nanoparticle stability. VSM analysis indicated a slight decrease in saturation magnetism after coating (51.1 emu/g) compared to MNPs (57.4 emu/g). In vitro release studies demonstrated a higher release rate (83 %) of DOX-ASP-MNPs at pH 5.2, indicating their suitability for cancerous cells. Cytotoxicity assays on A-549 cancer cell lines showed a dose-dependent response. DAPI staining revealed that free DOX caused more DNA damage. Cellular uptake studies indicated a time-dependent uptake of DOX-ASP-MNPs, higher at 3 h compared to 1 h, though lower than free DOX uptake due to different uptake pathways. Apoptosis assays over 72 h showed similar apoptotic rates for DOX-ASP-MNPs and free DOX. These findings suggest that ASP-MNPs possess enhanced physicochemical properties and effective drug delivery capabilities, making them a promising candidate for different biomedical applications, particularly targeted cancer therapy.
  • Article
    Citation - WoS: 24
    Citation - Scopus: 23
    Polyethers Isolated From the Marine Actinobacterium Streptomyces Cacaoi Inhibit Autophagy and Induce Apoptosis in Cancer Cells
    (Elsevier, 2019) Khan, Nasar; Yılmaz, Sinem; Aksoy, Semiha; Uzel, Ataç; Tosun, Çiğdem; Ballar Kırmızıbayrak, Petek; Bedir, Erdal
    Polyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1-3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies. As several polyether compounds with structural similarity such as monensin have been linked with autophagy and cell death, we first assessed the cytotoxicity of these three compounds. Compounds 2 and 3, but not 1, were found to be cytotoxic in several cell lines with a higher potency towards cancer cells. Furthermore, 2 and 3 caused accumulation of both autophagy flux markers LC3-II and p62 along with cleavage of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1 (PARP-1). Interestingly, prolonged treatment of the compounds caused a dramatic downregulation of the proteins related to autophagasome formation in a dose dependent manner. Our findings provide insights on the molecular mechanisms of the polyether-type polyketides, and signify their potency as chemotherapeutic agents through inhibiting autophagy and inducing apoptosis.
  • Article
    Citation - WoS: 9
    Citation - Scopus: 9
    Synergistic apoptotic effects of bortezomib and methylstat on multiple myeloma cells
    (Elsevier, 2020) Kaci, Fatma Necmiye; Kiraz, Yağmur; Çekdemir, Demet; Baran, Yusuf
    Background. In this study, we aimed to determine synergistic apoptotic and cytotoxic effects of methylstat and bortezomib on U266 and ARH77 multiple myeloma (MM) cells. Methods. Cytotoxic effects of the drugs were demonstrated by MTT cell proliferation assay while apoptotic effects were examined by loss of mitochondrial membrane potential (MMP) by JC-1 MMP detection kit, changes in caspase-3 enzyme activity and Annexin-V apoptosis assay by flow cytometry. Expression levels of apoptotic and antiapoptotic genes were examined by qRT-PCR. Results. Our results showed that combination of methylstat and bortezomib have synergistic antiproliferative effect on MM cells as compared to either agent alone. These results were also confirmed by showing synergistic apoptotic effects determined by increased loss of mitochondrial membrane potential and increased caspase-3 enzyme activity and relocation of phosphotidyleserine on the cell membrane by Annexin-V/PI double staining. Combination of bortezomib with methylstat arrested cells at the S phase of the cell cycle. Methylstat treatment caused upregulation of FASLG, NGFR, TNF, TNI-RS10B and TNFRS1B apoptotic genes and downregulation of AKT1, AVEN, BAG1 BCL2L2 and RELA antiapoptotic genes in a dose and time dependent manner. Conclusion. In conclusion, our data suggested that bortezomib in combination with methylstat decreased cell proliferation and induced apoptosis significantly in U266 and ARH77 cells. When supported with in vivo analyses, methylstat might be considered as a potential new agent for the treatment of MM. (C) 2020 IMSS. Published by Elsevier Inc.