High-throughput screening of FDA-approved drugs identifies colchicine as a potential therapeutic agent for atypical teratoid/rhabdoid tumors (AT/RTs)
4
Issued Date
2025-04-17
Resource Type
eISSN
20462069
Scopus ID
2-s2.0-105003434162
Journal Title
RSC Advances
Volume
15
Issue
16
Start Page
12331
End Page
12341
Rights Holder(s)
SCOPUS
Bibliographic Citation
RSC Advances Vol.15 No.16 (2025) , 12331-12341
Suggested Citation
Kanjanasirirat P., Jearawuttanakul K., Seemakhan S., Borwornpinyo S., Wongtrakoongate P., Hongeng S., Charoensutthivarakul S. High-throughput screening of FDA-approved drugs identifies colchicine as a potential therapeutic agent for atypical teratoid/rhabdoid tumors (AT/RTs). RSC Advances Vol.15 No.16 (2025) , 12331-12341. 12341. doi:10.1039/d5ra01341k Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109918
Title
High-throughput screening of FDA-approved drugs identifies colchicine as a potential therapeutic agent for atypical teratoid/rhabdoid tumors (AT/RTs)
Corresponding Author(s)
Other Contributor(s)
Abstract
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and aggressive tumor of the primary central nervous system primarily affecting children. It typically originates in the cerebellum and brain stem and is associated with a low survival rate. While standard chemotherapy has been used as a primary treatment for AT/RTs, its success rate is unsatisfactory, and patients often experience severe side effects. Therefore, there is an urgent need to develop new and effective treatment strategies. One promising approach for identifying new therapies is drug repurposing. Although many FDA-approved drugs have been repurposed for various cancers, there have been no reports of such applications for AT/RTs. In this study, a library of 2130 FDA-approved drugs was screened using a high-throughput screening system against 2D traditional cultures and 3D spheroid cultures of AT/RT cell lines (BT-12 and BT-16). From this screening, colchicine, a non-chemotherapeutic agent, was identified as a promising candidate. It exhibited IC50 values of 0.016 and 0.056 μM against 2D BT-12 and 2D BT-16 cells, respectively, and IC50 values of 0.004 and 0.023 μM against 3D BT-12 and BT-16 spheroid cultures. Additionally, the cytotoxic effects of colchicine on human brain endothelial cells and human astrocytes were evaluated, and CC50 > 20 μM was observed, which is over two orders of magnitude higher than its effective concentrations in AT/RT cells, indicating considerably lower toxicity to normal brain cells and brain endothelial cells. In conclusion, colchicine shows significant potential to be repurposed as a treatment for AT/RTs, providing a safer and more effective therapeutic option for this rare and challenging disease.