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    Anti-cancer activity of naringenin loaded smart polymeric nanoparticles in breast cancer
    (Elsevier, 2022) Yildirim, Metin; Acet, Omur; Yetkin, Derya; Acet, Burcu Onal; Karakoc, Veyis; Odabasi, Mehmet
    Breast cancer is the most common form of cancer among women worldwide, and approximately comprise 25% of all female malignancies. Naringenin (Nar) is a promising anticancer agent for breast cancer. However, its use as a therapeutic agent is limited due to its poor water solubility and bioavailability. The purpose of the present study is to prepare pH and thermo sensitive smart polymeric nanoparticles carrying naringenin (NarSPNPs) to improve bioavailability, and increase therapeutic efficacy against breast cancer. N-isopropylacrylamide and Vinyl imidazole were used as thermo and pH sensitive monomers, respectively. NarSPNPs were characterized using dynamic light scattering (DLS) analyses, SEM and FTIR for particle size and potential analysis, surface morphology and functional group determinations, respectively. Release profile and its effects on cell proliferation, apoptosis and cell cycle in breast cancer were also studied. Physicochemical characterization of newly prepared NarSPNPs, cytotoxicity, and IC50 assessments confirmed their stability and bioactivity as an anti-breast cancer agent with no toxicity against human epithelia cells. These findings together with flow cytometry analysis, revealed that apoptosis is the main mechanism underlying cell death after NarSPNPs treatment.
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    Biologically active sodium pentaborate pentahydrate and Hypericum perforatum oil loaded polyvinyl alcohol: chitosan membranes
    (Elsevier, 2024) Oztas, Necla; Kara, Eray; Demir, Didem; Yetkin, Derya; Ceylan, Seda; Iyiguendogdu, Zeynep
    In this study, sodium pentaborate pentahydrate (NaB) and Hypericum perforatum (HP) oil were incorporated into polyvinyl alcohol (PVA) and chitosan (CH) polymer blend to obtain membranes by solution casting method. In order to see the synergistic effects of NaB and HP oil on the biological and physical properties of the membranes NaB and HP oil were incorporated into membrane matrix in different ratios. Fourier-transform infrared spectroscopy (FTIR) results showed that no significant bond formation between the bioactive components and the PVA:CH matrix. According to mechanical test results, Young's Modulus and elongation at break decreased from 426 MPa to 346 MPa and 52.23 % to 15.11 % for neat PVA:CH membranes and NaB and HP oil incorporated PVA:CH (PVA:CH@35NaB:HP) membranes, respectively. Antimicrobial activity tests have shown the membranes were over 99 % effective against Escherichia coli, Staphylococcus aureus, and Candida albicans, underlining their potential for infection control. Cytocompatibility assay performed with Human Dermal Fibroblast (HDFa) cells highlight the biocompatibility of the membranes, revealing 74.84 % cell viability after 72 h. The properties of NaB and HP oil doped PVA:CH based membranes obtained from these experiments reveal the promise of a versatile membrane for applications in wound healing, tissue engineering and other biomedical fields.
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    N-(benzazol-2-yl)-2-substituted phenylacetamide derivatives: Design, synthesis and biological evaluation against MCF7 breast cancer cell line
    (Elsevier, 2023) Zoatier, Bayan; Yildirim, Metin; Alagoz, Mehmet Abdullah; Yetkin, Derya; Turkmenoglu, Burcin; Burmaoglu, Serdar; Algul, Oztekin
    This work describes the straightforward and efficient one-pot synthesis of a new library of N-(benzazol-2-yl)-2-substituted phenylacetamide derivatives (19-27). Using the MTT assay, these compounds were evaluated for their in vitro anticancer activity against the MCF7 human breast cancer cell line, and the results were compared to the standard doxorubicin. The majority of compounds exhibited an inhibitory effect against the cancer cell line, with compounds 19, 22, and 26 exhibiting exceptional cytotoxicity against MCF7 cells. Using flow cytometry, the most potent compound 19 on the induction of apoptosis in the breast cancer cell line was determined. Compound 19 induced G1-phase cell cycle arrest followed by apoptotic cell death. In silico analyses of potent compounds 19, 22, and 26 were conducted to investigate their interactions with Human DNA topoisomerase II. The energy calculations were found to be in excel-lent agreement with the calculated IC50 values. In addition, drug similarity parameter values for the three active compounds were determined using in silico ADME prediction studies. Considering all of these re-sults, it appears that these N-(benzazol-2-yl)-2-substituted phenylacetamide derivatives may be effective anticancer agents. This work may possibly generate new concepts for the enhancement of inhibitors of human DNA topoisomerase II for breast cancer treatment.(c) 2023 Elsevier B.V. All rights reserved.
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    Non-canonical anti-cancer, anti-metastatic, anti-angiogenic and immunomodulatory PDT potentials of water soluble phthalocyanine derivatives with imidazole groups and their intracellular mechanism of action
    (Elsevier, 2022) Ayaz, Furkan; Yetkin, Derya; Yuzer, Abdulcelil; Demircioglu, Kubra; Ince, Mine
    Cancer is currently a leading health issue globally. Chemotherapy is a prominent treatment method but due to undesired side effects t, there has been a need for novel less toxic approaches. Photodynamic therapy may be listed among the alternatives for efficient and potentially less detrimental applications of cancer therapy. Canonical photodynamic therapy (PDT) approach requires a light source with a specific wavelength of light, a nontoxic photosensitizer and molecular oxygen. PDT creates the desired effect by the photochemical reaction created through interaction of these components to create reactive oxygen species that will act on the cancer cells to enable anti-cancer activities. In our study we focus on non-canonical PDT application. In this approach we are not only aiming to eliminate cancer cells in the environment but also test the anti-metastatic, anti-angiogenic and possible immunomodulatory activities of the novel photosensitizers. Moreover, in our approach, we studied the intracellular pathways that are crucial for carcinogenesis, cell cycle, apoptosis, angiogenesis, metastasis and immune function to decipher the mechanism of the action for each compound. Reactive oxygen species based explanation was not valid in our study, hence it brings out a non canonical approach to PDT applications. Our results suggests that Phthalocyanine derivatives with imidazole groups can be effectively used against lung, colon, breast and prostate cancer while differentially effecting metastasis, angiogenesis, cell cycle, apoptosis and immune system cell's activities. Based on the results, PDT application of these phthalocyanine derivatives can be an effective treatment option to replace chemotherapy to minimize the potential side effects.