دورية أكاديمية
TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells
العنوان: | TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells |
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المؤلفون: | Kun-Ming Wu MD, Chih-Wen Chi PhD, Jerry Cheng-Yen Lai PhD, Yu-Jen Chen MD, PhD, Yu Ru Kou PhD |
المصدر: | Cancer Control, Vol 27 (2020) |
بيانات النشر: | SAGE Publishing, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. In this study, its effect on A549 and H838 human non-small cell lung cancer (NSCLC) cells was investigated. Cell viability and proliferation were determined by thiazolyl blue tetrazolium bromide and clonogenic assays, respectively, and cell cycle analysis and detection of phosphorylated histone H3 (Ser10) were performed by flow cytometry. γ-H2AX protein; G2/M phase-associated molecules ataxia-telangiectasia mutated (ATM), CHK1, CHK2, CDC25C, CDC2, and cyclin B1; and apoptosis were assessed with immunofluorescence staining, immunoblotting, and an annexin V assay, respectively. The effect of co-treatment with CHIR124 (a checkpoint kinase 1 [CHK1] inhibitor) was also studied. TLC388 decreased the viability and proliferation of cells of both NSCLC lines in a dose-dependent manner. TLC388 inhibited the viability of NSCLC cell lines with an estimated concentration of 50% inhibition (IC50), which was 4.4 and 4.1 μM for A549 and H838 cells, respectively, after 24 hours. Moreover, it resulted in the accumulation of cells at the G2/M phase and increased γ-H2AX levels in A549 cells. Levels of the G2 phase–related molecules phosphorylated ATM, CHK1, CHK2, CDC25C, and cyclin B1 were increased in TLC388-treated cells. CHIR124 enhanced the cytotoxicity of TLC388 toward A549 and H838 cells and induced apoptosis of the former. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1073-2748 10732748 |
Relation: | https://doaj.org/toc/1073-2748 |
DOI: | 10.1177/1073274819897975 |
URL الوصول: | https://doaj.org/article/c99f74ce3f0e49a48c17888e7e907ac7 |
رقم الأكسشن: | edsdoj.99f74ce3f0e49a48c17888e7e907ac7 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 10732748 |
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DOI: | 10.1177/1073274819897975 |