Anti-tumor Effects of Idarubicin Hydrochloride in Desmoid Tumors.

Autor:	Lee Y; Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology (UST), Daejeon, Republic of Korea., Kim Y; Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea., Shin H; Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.; Department of Biotechnology, Yonsei University, Seoul, Republic of Korea., Ryu YC; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea., Kang DW; Medpacto Inc., Seoul, Republic of Korea., Kim TI; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea., Cho YH; Drug Discovery Platform Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea; y-hcho@krict.re.kr.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology (UST), Daejeon, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Anticancer research [Anticancer Res] 2024 Dec; Vol. 44 (12), pp. 5313-5322.
DOI:	10.21873/anticanres.17359
Abstrakt:	Background/aim: Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs. Materials and Methods: Mouse models with Apc mutations, specifically Apc 1638N/+ and Apc 1638N/+ /Trp53 -/- , were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc 1638N/+ mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells. Results: The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc 1638N/+ and Apc 1638N/+ /Trp53 -/- cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc 1638N/+ mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model. Conclusion: IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II. (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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