Cytotoxic and apoptotic effects of trabectedin on breast cancer stem cells; [Trabektedinin meme kanseri kök hücreleri üzerindeki sitotoksik ve apoptotik etkileri]
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Date
2019
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Abstract
Objective: In this study, effect of trabectedin (ET743, Yondelis®) was investigated on the viability of MCF-7 cells and CD44+/CD24- breast cancer stem cells. Material and Methods: CD44+/CD24- breast cancer stem cells were isolated from MCF-7 cells by using flow cytometry. XTT test was used to investigate the effect of trabectedin on the viability of MCF-7 and CD44+/ CD24- breast cancer stem cells. Apoptotic effect of trabectedin was investigated by measuring DNA fragmentation and changes in mitochondrial membrane potential were determined by tetram-ethylrhodamine ethyl ester (TMRE) staining. Results: Trabectedin inhibited the cell viability of both MCF-7 breast cancer and CD44+/CD24- breast cancer stem cells in a concentration and time dependent manner. IC50 concentrations at 48 h was calculated as 4.52±0.7 nM for MCF-7 cells and 1.23±1.2 nM for CD44+/CD24- cells. It was found that breast cancer stem cells were more sensitive to trabectedin than MCF-7 cancer cells. Cells in control group were stained with fluorescent TMRE stain but the staining was less in the both cell groups that were treated with the IC50 concentrations of trabectedin. It was shown that trabectedin induced more apoptotic cells in CD44+/CD24- breast cancer stem cells. Conclusion: According to the current data, it was shown that trabectedin induced cytotoxicity and apoptosis in breast cancer stem cells as well as MCF-7 cancer cells in a concentration and time dependent manner. These data indicates that trabectedin might be a potential therapeutic for breast cancer. However, more detailed studies investigating the effects of trabectedin on breast cancer stem cells are needed. © 2019 by Türkiye Klinikleri.
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antineoplastic agent , tetramethylrhodamine ethyl ester , trabectedin , antineoplastic activity , apoptosis , Article , breast cancer , cancer stem cell , cancer therapy , cell viability , controlled study , cytotoxicity , DNA fragmentation , dose response , flow cytometry , human , human cell , IC50 , MCF-7 cell line , mitochondrial membrane potential , XTT assay