AI Article Synopsis
- A research study focused on glioma-initiating cells, which help glioblastomas resist treatment and explore a new therapeutic option through drug repositioning.
- The researchers screened over 1300 drugs and found that pentamidine, an antibiotic, successfully inhibited the growth and self-renewal of glioma-initiating cell lines and showed positive effects on other glioblastoma lines.
- Pentamidine was effective in both lab studies and a mouse model, demonstrating its potential as a promising treatment for glioblastomas by targeting multiple cell types and mechanisms.
Article Abstract
Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug reposition, we investigated a therapeutic drug for glioma-initiating cells. Drug screening was undertaken to select candidate agents that inhibit proliferation of two different glioma-initiating cells lines. The alteration of proliferation and stemness of the two glioma-initiating cell lines, and proliferation, migration, cell cycle, and survival of these two differentiated glioma-initiating cell lines and three different glioblastoma cell lines treated with the candidate agent were evaluated. We also used a xenograft glioma mouse model to evaluate anticancer effects of treated glioma cell lines. Among the 1301 agents, pentamidine-an antibiotic for Pneumocystis jirovecii-emerged as a successful antiglioma agent. Pentamidine treatment suppressed proliferation and stemness in glioma-initiating cell lines. Proliferation and migration were inhibited in all differentiated glioma-initiating cells and glioblastoma cell lines, with cell cycle arrest and caspase-dependent apoptosis induction. The in vivo study reproduced the same findings as the in vitro studies. Pentamidine showed a stronger antiproliferative effect on glioma-initiating cells than on differentiated cells. Western blot analysis revealed pentamidine inhibited phosphorylation of signal transducer and activator of transcription 3 in all cell lines, whereas Akt expression was suppressed in glioma-initiating cells but not in differentiated lines. In the present study, we identified pentamidine as a potential therapeutic drug for glioma. Pentamidine could be promising for the treatment of glioblastomas by targeting both glioma-initiating cells and differentiated cells through its multifaceted antiglioma effects.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323113 | PMC |
| http://dx.doi.org/10.1111/cas.15827 | DOI Listing |
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