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Open AccessArticle

An Isoxazole Derivative SHU00238 Suppresses Colorectal Cancer Growth through miRNAs Regulation

1,2,†, 2,†, 1, 1, 2, 1,3,* and 2,*
1
Department of Chemistry, Qianweichang College, Shanghai University, Shanghai 200444, China
2
School of Life Science, Shanghai University, Shanghai 200444, China
3
Innovative Drug Research Center, Shanghai University, Shanghai 200444, China
*
Authors to whom correspondence should be addressed.
These two authors contributed equally to this work.
Academic Editor: Yasuyoshi Miyata
Molecules 2019, 24(12), 2335; https://doi.org/10.3390/molecules24122335
Received: 12 June 2019 / Revised: 22 June 2019 / Accepted: 25 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Anti-Cancer Drug: Discovery, Development and Combination)
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Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Isoxazoline and isoxazole derivatives represent an important class of five-membered heterocycles, which play a pivotal role in drug discovery. In our previous study, we developed a series of isoxazole derivatives with an efficient method. In this study, we evaluated their effects on tumor cell growth. HCT116 cells were treated with isoxazole derivatives; an cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 (half maximal inhibitory concentration) of each derivative. Compound SHU00238, which was obtained by the copper nitrate-mediated [2+2+1] cycloaddition reaction of olefinic azlactone with naphthalene-1,4-dione, has a lower IC50; we analyzed its inhibitory activity in further assays. Cell apoptosis was estimated by flow cytometry analysis in vitro. SHU00238 injection was used to treat tumor-bearing mice. We found that SHU00238 suppressed cell viability and promoted cell apoptosis in vitro. SHU00238 treatment significantly inhibited colonic tumor growth in vivo. Furthermore, we compared the miRNAs expression changes in HCT116 cells before and after SHU00238 treatment. MiRNA profiling revealed that SHU00238 treatment affected cell fate by regulating a set of miRNAs. In conclusion, SHU00238 impedes CRC tumor cell proliferation and promotes cell apoptosis by miRNAs regulation. View Full-Text
Keywords: colorectal cancer; isoxazole derivative; miRNAs; SHU00238; drug discovery colorectal cancer; isoxazole derivative; miRNAs; SHU00238; drug discovery
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Wang, H.; Ma, Y.; Lin, Y.; Liu, J.; Chen, R.; Xu, B.; Liang, Y. An Isoxazole Derivative SHU00238 Suppresses Colorectal Cancer Growth through miRNAs Regulation. Molecules 2019, 24, 2335.

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