Browsing by Author "Tuncel, Ozge"

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Citation - WoS: 2
Development of AB3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated with Triphenylphosphonium for Higher Photodynamic Efficacy
(Amer Chemical Soc, 2022) Onal, Emel; Tuncel, Ozge; Vatansever, Ipek Erdogan; Albakour, Mohamad; Celik, Gizem Gumusgoz; Kucuk, Tugba; Ozcelik, Serdar
There are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluores-cence quantum yields (phi F) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (phi Delta) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB3TPP-Pc, AB3TPP-Por-C4, and AB3TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB3TPP-Por-C4, AB3TPP-Por-C6, and AB3TPP-Pc compounds compared to the reference molecules ZnPc and H2TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB3TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.
Citation - WoS: 9
Genomewide m⁶A Mapping Uncovers Dynamic Changes in the m⁶A Epitranscriptome of Cisplatin-Treated Apoptotic HeLa Cells
(Mdpi, 2022) Alasar, Azime Akcaoz; Tuncel, Ozge; Gelmez, Ayse Bengisu; Saglam, Buket; Vatansever, Ipek Erdogan; Akgul, Bunyamin; Akgül, Bünyamin
Cisplatin (CP), which is a conventional cancer chemotherapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the m(6)A methylome are unknown. We employed an m(6)A miCLIP-seq approach to investigate the effect of m(6)A methylation marks under cisplatin-mediated apoptotic conditions on HeLa cells. Our high-resolution approach revealed numerous m(6)A marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. We tracked the fate of differentially methylated candidate mRNAs under METTL3 knockdown and cisplatin treatment conditions. Polysome profile analyses revealed perturbations in the translational efficiency of PMAIP1 and PHLDA1 transcripts. Congruently, PMAIP1 amounts were dependent on METTL3. Additionally, cisplatin-mediated apoptosis was sensitized by METTL3 knockdown. These results suggest that apoptotic pathways are modulated by m(6)A methylation events and that the METTL3-PMAIP1 axis modulates cisplatin-mediated apoptosis in HeLa cells.
Citation - WoS: 9
Citation - Scopus: 9
Noncoding RNAs in apoptosis: identification and function
(Tubitak Scientific & Technological Research Council Turkey, 2022) Tuncel, Ozge; Kara, Merve; Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, Bünyamin
Apoptosis is a vital cellular process that is critical for the maintenance of homeostasis in health and disease. The derailment of apoptotic mechanisms has severe consequences such as abnormal development, cancer, and neurodegenerative diseases. Thus, there exist complex regulatory mechanisms in eukaryotes to preserve the balance between cell growth and cell death. Initially, protein coding genes were prioritized in the search for such regulatory macromolecules involved in the regulation of apoptosis. However, recent genome annotations and transcriptomics studies have uncovered a plethora of regulatory noncoding RNAs that have the ability to modulate not only apoptosis but also many other biochemical processes in eukaryotes. In this review article, we will cover a brief summary of apoptosis and detection methods followed by an extensive discussion on microRNAs, circular RNAs, and long noncoding RNAs in apoptosis.