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Colchicine as a novel drug for the treatment of osteosarcoma through drug repositioning based on an FDA drug libraryoa mark
  • Oh, Jisun ;
  • An, Hyun−Ju ;
  • Yeo, Hyun Jeong ;
  • Choi, Sujin ;
  • Oh, Jisu ;
  • Kim, Segi ;
  • Kim, Jin Man ;
  • Choi, Junwon ;
  • Lee, Soonchul
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Publication Year
2022-08-18
Journal
Frontiers in Oncology
Publisher
Frontiers Media S.A.
Citation
Frontiers in Oncology, Vol.12
Keyword
colchicinedrug repositioningFDA-approved drugsSaos-2U2OS
All Science Classification Codes (ASJC)
OncologyCancer Research
Abstract
Background: Colchicine is a traditional medication that is currently approved to treat gout and familial Mediterranean fever (FMF). However, colchicine has a wide range of anti-inflammatory activities, and several studies have indicated that it may be useful in a variety of other conditions, such as rheumatic disease, cardiac disease, and cancer. Osteosarcoma, the most common type of bone sarcoma, is derived from primitive bone-forming mesenchymal cells. In this study, we investigated whether colchicine could be used to treat osteosarcoma through the regulation of cell cycle signaling. Methods: Two human osteosarcoma cell lines, U2OS and Saos-2, were used. A clonogenic assay was used to determine the antiproliferative effects of colchicine on osteosarcoma cells. Reactive oxygen species (ROS) production and apoptosis were measured by flow cytometry. Migration and invasion assays were performed to investigate the inhibitory effects of colchicine. The signaling pathways related to colchicine treatment were verified by GO biological process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: Colchicine was selected as the lead compound based on the results of initial screening and cell viability assays conducted in Saos-2 and U2Os cells. Colchicine reduced the viability of Saos-2 and U2OS cells in a concentration-dependent manner. It also significantly inhibited colony-forming ability and induced ROS production and apoptosis. It also inhibited the migration and invasion of both Saos-2 and U2OS cells. GOBP and KEGG enrichment analyses indicated the involvement of microtubule-based processes and cancer-related pathways. Conclusions: These findings suggest that colchicine has therapeutic potential in osteosarcoma.
ISSN
2234-943X
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/32907
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85137726918&origin=inward
DOI
https://doi.org/10.3389/fonc.2022.893951
Journal URL
http://www.frontiersin.org/Oncology/about
Type
Article
Funding
This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute. It was funded by the Ministry of Health and Welfare, Republic of Korea (grant number HI16C1559), and by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Nos. NRF-2021R1A4A3023587 and 2022R1A2C2005916).
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Choi, Jun Won최준원
College of Bio-convergence Engineering
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