Abstract
Gliomas, the most malignant form of brain tumors, contain a small subpopulation of glioma stem cells (GSCs) that are implicated in therapeutic resistance and tumor recurrence. Topoisomerase I inhibitors, shikonin and topotecan, play a crucial role in anti-cancer therapies. After isolated and identified the GSCs from glioma cells successfully, U251, U87, GSCs-U251 and GSCs-U87 cells were administrated with various concentrations of shikonin or topotecan at different time points to seek for the optimal administration concentration and time point. The cell viability, cell cycle and apoptosis were detected using cell counting kit-8 and flow cytometer to observe the inhibitory effects on glioma cells and GSCs. We demonstrated that shikonin and topotecan obviously inhibited proliferation of not only human glioma cells but also GSCs in a dose- and time-dependent manner. According to the IC50 values at 24 h, 2 μmol/L of shikonin and 3 μmol/L of topotecan were selected as the optimal administration concentration. In addition, shikonin and topotecan induced cell cycle arrest in G0/G1 and S phases and promoted apoptosis. The down-regulation of Bcl-2 expression with the activation of caspase 9/3-dependent pathway was involved in the apoptosis process. Therefore, the above results showed that topoisomerase I inhibitors, shikonin and topotecan, inhibited growth and induced apoptosis of GSCs as well as glioma cells, which suggested that they might be the potential anticancer agents targeting gliomas to provide a novel therapeutic strategy.
Highlights
Glioma is one of the most common malignant brain tumors in adults
The result showed that the isolated glioma stem cells (GSCs) using sphere culture contained 98.2% and 98.6% CD133+ cells in GSCs-U251 and GSCs-U87, respectively (Figure 1C)
We revealed that shikonin or topotecan inhibited the proliferation of the GSCs as well as the glioma cells in a dose- and timedependent manner
Summary
Glioma is one of the most common malignant brain tumors in adults. Over recent years, more and more studies have pointed out that the fatal nature of glioma is caused by glioma stem cells (GSCs), which are present in glioma. Some reports showed that recurrent human colorectal cancer biopsies and breast cancer stem cells contained significantly higher levels of Topo I than normal tissues [5,6]. Topo I inhibitors can be divided into the Topo I poison and the suppressor types, both of which act at the level of the topoisomerase I-DNA complex and stimulate DNA cleavage. The Topo I poisons, like topotecan, act after the cleavage of DNA by the enzyme and inhibit the religation. The activity of Topo I suppressors is higher in tumor cells with low-expressed Topo I [9,10]. These two classes of inhibitor show separate mechanisms in anti-cancer treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
