IMR Press / FBL / Volume 27 / Issue 1 / DOI: 10.31083/j.fbl2701018
Open Access Original Research
Screening a redox library identifies the anti-tumor drug Hinokitiol for treating intrahepatic cholangiocarcinoma
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1 Faculty of Environmental and Life Sciences, Beijing University of Technology, 100124 Beijing, China
2 Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, 00850 Beijing, China
3 Academy of Military Medical Sciences (AMMS), Academy of Military Sciences, 100071 Beijing, China
4 The Second Medical Center, Chinese PLA General Hospital, 100853 Beijing, China
*Correspondence: Yxlong2000@bjut.edu.cn (Xinlong Yan); Yuewen0206@126.com (Wen Yue); Peixt@nic.bmi.ac.cn (Xuetao Pei)
These authors contributed equally.
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(1), 18; https://doi.org/10.31083/j.fbl2701018
Submitted: 28 August 2021 | Revised: 4 December 2021 | Accepted: 7 December 2021 | Published: 13 January 2022
(This article belongs to the Special Issue Recent Advances in Cancer Research and Environmental Toxicology)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Aims: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant and heterogeneous cancer with a poor prognosis. At present, there is no optimal treatment except for surgical resection, and recurrence after resection will lead to death due to multidrug resistance. Changes in the redox signal have been found to be closely related to the growth and drug resistance of tumor cells. Therefore, the purpose of this study was to screen small molecule compounds from the redox library to find a drug for anti-ICC and to explore its downstream mechanism. Material and methods: Tumor clone and sphere formation of ICC cell lines, as well as mouse ICC organoid proliferation assays were utilized to screen the candidate drug in the Redox library. Western blotting, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), as well as cell apoptosis and cell cycle flow cytometry assays were used to explore the mechanism. Results: We found that Hinokitiol was a candidate drug through inhibition of tumor clone and sphere formation, and the expression of cancer stem cell (CSC)-related genes. Furthermore, Hinokitiol significantly inhibited the proliferation of ICC cells by downregulating the ERK and P38 pathways. In addition, the combination of Hinokitiol and Palbociclib showed a significant inhibitory effect on human ICC cells and mouse ICC organoids. Conclusion: Hinokitiol may have the potential to be developed as a clinical therapeutic drug for ICC treatment.

Keywords
Redox library
Intrahepatic cholangiocarcinoma
Hinokitiol
Proliferation
Tumor sphere
Tumor organoids
Figures
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