PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article K41-A Enhances the Antiproliferative Efficacy of Cisplatin in Neuroblastoma by Modulating Apoptosis and Autophagy(Oxford University Press, 2026) Sanlav, Gamze; Kum Ozsengezer, Selen; Altun, Zekiye; Bedir, Erdal; Aktas, Safiye; Olgun, NurObjectives Neuroblastoma (NB), the most common extracranial tumor in childhood, has a poor prognosis, especially in cases with MYC gene amplification. Cisplatin (CDDP) is widely used in treatment, but its effectiveness is limited due to chemotherapy resistance. Autophagy plays a dual role in cancer progression, either promoting survival or contributing to cell death.Methods This study explores the anticancer effects of K41-A, a polycyclic polyether molecule, alone and in combination with CDDP in SH-SY5Y and KELLY NB cell lines, the HE-IOC1 noncancerous cochlear cell line, and the NB xenograft model.Key findings For the first time, we demonstrate that K41-A, either alone or combined with CDDP, significantly inhibits cell proliferation selectively in NB cells, sparing noncancerous cells. This study confirmed that K41-A alone and in combination with CDDP induced changes in both apoptotic and autophagic cell death components in NB, resulting in antiproliferative activity in vitro and in vivo. In addition, the combination with CDDP enhanced the therapeutic efficacy of K41-A.Conclusions These results highlight the potential of K41-A as a candidate drug for the treatment of NB.Article Citation - WoS: 8Protective and Therapeutic Effects of Milrinone on Acoustic Trauma in Rat Cochlea(Springer, 2019) Ceylan, Seyit Mehmet; Uysal, Erdal; Altinay, Serdar; Sezgin, Efe; Bilal, Nagihan; Petekkaya, Emine; Gulbagci, Mustafa EmreObjectiveThe aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis.MethodsA total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25mg/kg) in which milrinone was administered 1h before acoustic trauma (AT) and 2h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50mg/kg) in which the drug was administered 1h before AT and 2h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining.ResultsIn terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p>0.05). After 5days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p>0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p<0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p<0.0001).ConclusionWe reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.Article Citation - WoS: 6Citation - Scopus: 6Biomolecular Fingerprints of the Effect of Zoledronic Acid on Prostate Cancer Stem Cells: Comparison of 2d and 3d Cell Culture Models(Academic Press Inc., 2024) Güler,G.; Acikgoz,E.; Mukhtarova,G.; Oktem,G.Revealing the potential of candidate drugs against different cancer types without disrupting normal cells depends on the drug mode of action. In the current study, the drug response of prostate cancer stem cells (PCSCs) to zoledronic acid (ZOL) grown in two-dimensional (2D) and three-dimensional (3D) culture systems was compared using Fourier transform-infrared (FT-IR) spectroscopy which is a vibrational spectroscopic technique, supporting by biochemical assays and imaging techniques. Based on our data, in 2D cell culture conditions, the ZOL treatment of PCSCs isolated according to both C133 and CD44 cell surface properties induced early/late apoptosis and suppressed migration ability. The CD133 gene expression and protein levels were altered, depending on culture systems. CD133 expression was significantly reduced in 2D cells upon ZOL treatment. FT-IR data revealed that the integrity, fluidity, and ordering/disordering states of the cell membrane and nucleic acid content were altered in both 2D and 3D cells after ZOL treatment. Regular protein structures decrease in 2D cells while glycogen and protein contents increase in 3D cells, indicating a more pronounced cytotoxic effect of ZOL for 2D cells. Untreated 3D PCSCs exhibited an even different spectral profile associated with IR signals of lipids, proteins, nucleic acids, and glycogen in comparison to untreated 2D cells. Our study revealed significant differences in the drug response and cellular constituents between 2D and 3D cells. Exploring molecular targets and/or drug-action mechanisms is significant in cancer treatment approaches; thus, FT-IR spectroscopy can be successfully applied as a novel drug-screening method in clinical research. © 2024 Elsevier Inc.Book Part Citation - Scopus: 5Epitranscriptomics Changes the Play: M6a Rna Modifications in Apoptosis(Springer, 2022) Akçaöz, Azime; Akgül, BünyaminApoptosis is a form of programmed cell death that is essential for cellular and organismal homeostasis. Any irregularities that disturb the balance between apoptosis and cell survival have severe implications, such as improper development or life-threatening diseases. Thus, it is highly critical to maintain a proper rate of apoptosis throughout development. In fact, several complex transcriptional and posttranscriptional mechanisms exist in eukaryotes to critically regulate the rate of apoptotic processes. Recent studies suggest that not only RNA sequences but also their modifications, such as m6A methylation, play a fundamental role in these transcriptional and posttranscriptional processes. A specific set of proteins, called writer, eraser, and reader of m6A marks, modulate the rate of apoptosis by determining the m6A repertoire and the fate of certain transcripts associated with apoptosis. In this Review, we will cover the dynamic m6A RNA modifications and their impact on modulation of apoptosis.Article Citation - WoS: 2Citation - Scopus: 2Effects of Golden Thistle (scolymus Hispanicus L.) on Cytotoxic Activity: Cell Cycle Arrest and Apoptotic Properties on the Caco-2 Cell Line(Mary Ann Liebert Inc., 2022) Özel Taşcı, Cansu; Güleç, ŞükrüCancer is a global concern for many individuals with high mortality rates, with colon cancer being the third most common diagnosed cancer worldwide. A phytochemical-rich diet is often recommended in the prevention and during the treatment of cancer cases. Golden thistle (GT) plant (Scolymus hispanicus L.) is a wild edible plant widely consumed in the Mediterranean countries. In this study, we aimed to obtain a hydromethanolic extract from three parts of the GT plant and test its antiproliferative activity in the CaCo-2 human adenocarcinoma cell line. Concentrations of the golden thistle extract (GTE) were used to treat CaCo-2 cells and the most significant reduction was detected with 4 mg/mL GTE after 72 h, with 78.3% decrease in cell viability (P < .05). Additionally, 4 mg/mL GTE caused 7.8-fold higher release of lactate dehydrogenase enzyme, indicating cell death after treatment. Flow cytometric analyses concluded both 3.3-fold higher early and late apoptotic activity of the 4 mg/mL GTE compared with the nontreated control group (P < .05). Last, 4 mg/mL GTE showed 24.1% reduction in the G1 phase and 38.1% increase in the S phase of cell cycle distribution. The alteration of G1 and S phases in the cell cycle led to growth reduction of CaCo-2 cells and caused apoptosis. Copyright