Browsing by Subject "cell cycle G1 phase"

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    Trabectedin (ET-743) in prostate cancer: Endoplasmic reticulum stress-induced apoptotic effect
    (John Wiley and Sons Inc, 2022) Atmaca H.; Oğuz F.; Ilhan S.
    Trabectedin is a chemotherapy agent originating from a tunicate, Ecteinascidia turbinata. In this study, DNA-independent action mechanisms of trabectedin are investigated in prostate cancer (PCa) cells. Cell viability was assessed via XTT assay. Apoptosis was evaluated via flow cytometry. Tetramethylrodamine ethyl ester (TMRE) dye was utilized to determine mitochondrial membrane potential (MMP). Cell cycle distribution was investigated via flow cytometric analysis. Reactive oxygen species (ROS) were monitored using fluorescence CM-H2DCFDA dye. Changes in CHOP, p-eIF2α, GRP78 and p-PERK which are endoplasmic reticulum (ER) stress-involved proteins were investigated via western blot. Trabectedin induced cytotoxicity and cell cycle arrest at the G2/M phase. Trabectedin decreased MMP via ROS generation in PCa cells. ER stress-related proteins CHOP, p-eIF2α, GRP78 and p-PERK were also elevated by trabectedin treatment indicating the induction of ER stress-induced apoptosis. The results of this study show that trabectedin may be an effective chemotherapeutic for PCa. © 2022 Wiley-VCH GmbH.
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    N-Propargylic β-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses
    (John Wiley and Sons Inc, 2023) Ilhan S.; Atmaca H.; Yilmaz E.S.; Korkmaz E.; Zora M.
    Breast cancer is one of the most common cancers worldwide and the discovery of new cytotoxic agents is needed. Enaminones are regarded to be a significant structural motif that is found in a variety of pharmacologically active compounds however the number of studies investigating the anticancer activities of N-propargylic β-enaminones (NPEs) is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs (1-23) on human breast cancer cells. Cytotoxicity was evaluated via MTT assay. Apoptotic cell death and cell cycle distributions were investigated by flow cytometry. CM-H2DCFDA dye was used to evaluate cellular ROS levels. Expression levels of Bcl-2, Bax, p21, and Cyclin D1 were measured by quantitative real-time PCR. ADME properties were calculated using the ADMET 2.0 tool. NPEs 4, 9, 16, and 21 showed selective cytotoxic activity against breast cancer cells with SI values >2. NPEs induced apoptosis and caused significant changes in Bcl-2 and Bax mRNA levels. The cell cycle was arrested at the G0/G1 phase and levels of p21 and Cyclin D1 were upregulated in both breast cancer cells. ROS levels were significantly increased by NPEs, suggesting that the cytotoxic and apoptotic effects of NPEs were mediated by ROS. ADME analysis revealed that NPEs showed favorable distributions in both breast cancer cell lines, meaning good lipophilicity values, low unfractionated values, and high bioavailability. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed. © 2023 Wiley Periodicals LLC.