Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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

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Author: search.filters.author.Çağır, AliPublisher: search.filters.publisher.Elsevier

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  • Article
    Citation - WoS: 10
    Citation - Scopus: 11
    A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices
    (Elsevier, 2020) Gökçe, Begüm; Akçok, İsmail; Çağır, Ali; Pesen Okvur, Devrim
    Drug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.
  • Article
    2’-Methylklavuzon Causes Lipid-Lowering Effects on A549 Non-Small Cell Lung Cancer Cells and Significant Changes on Dna Structure Evidenced by Fourier Transform Infrared Spectroscopy
    (Elsevier, 2020) Ceylan, Çağatay; Aksoy, Hatice Nurdan; Çağır, Ali; Çetinkaya, Hakkı
    Various chemical agents are used in the treatment of Non-Small Cell Lung Cancer (NSCLC). 2?-methylklavuzon was proposed as a potential chemotherapeutic agent in cancer treatment based on its topoisomerase inhibition activity. In this study the cellular effects of 2?-methylklavuzon was evaluated on A549 cancer cells using FTIR spectroscopy. 2?-methylklavuzon induced significant changes on both the whole cell lyophilizates and the lipid extracts of the A549 lung cancer cells. 2?-methylklavuzon caused significant structural changes in A549 cell DNA structure: T, A and G DNA breathing modes are lost after the drug application indicating the loss of topoisomerase activity. The level of transcription and RNA synthesis was enhanced. 2?-methylklavuzon induced single stranded DNA formation evidenced by the increase in the ratio of asymmetric/symmetric phosphate stretching modes. 2?-methylklavuzon induced band shifts only in the asymmetric mode of phosphate bonds not in the symmetrical phosphate bond stretching. 2?-methylklavuzon induced A form of DNA topography. In addition to the changes in the DNA structure and transcription 2?-methylklavuzon also caused lipid-lowering effect in A549 cancer cells. 2?-methylklavuzon suppressed lipid unsaturation, however, it induced formation of lipids with ring structures. 2?-methylklavuzon suppressed phosphate-containing lipids significantly and decreased carbonyl containing lipids and cholesterol slightly. 2?-methylklavuzon caused increases in the hydrocarbon chain length. Overall, 2?-methylklavuzon can be used as a lipid-lowering compound in the treatment of NSCLC and other cancer therapies. © 2020 Elsevier B.V.