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Issue 36, 2017
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Developing antineoplastic agents that target peroxisomal enzymes: cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)

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Abstract

Cytisine-linked isoflavonoids (CLIFs) inhibited PC-3 prostate and LS174T colon cancer cell proliferation by inhibiting a peroxisomal bifunctional enzyme. A pull-down assay using a biologically active, biotin-modified CLIF identified the target of these agents as the bifunctional peroxisomal enzyme, hydroxysteroid 17β-dehydrogenase-4 (HSD17B4). Additional studies with truncated versions of HSD17B4 established that CLIFs specifically bind the C-terminus of HSD17B4 and selectively inhibited the enoyl CoA hydratase but not the D-3-hydroxyacyl CoA dehydrogenase activity. HSD17B4 was overexpressed in prostate and colon cancer tissues, knocking down HSD17B4 inhibited cancer cell proliferation, suggesting that HSD17B4 is a potential biomarker and drug target and that CLIFs are potential probes or therapeutic agents for these cancers.

Graphical abstract: Developing antineoplastic agents that target peroxisomal enzymes: cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)

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Supplementary files

Article information


Submitted
29 Jun 2017
Accepted
24 Aug 2017
First published
24 Aug 2017

Org. Biomol. Chem., 2017,15, 7623-7629
Article type
Paper

Developing antineoplastic agents that target peroxisomal enzymes: cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)

M. S. Frasinyuk, W. Zhang, P. Wyrebek, T. Yu, X. Xu, V. M. Sviripa, S. P. Bondarenko, Y. Xie, H. X. Ngo, A. J. Morris, J. L. Mohler, M. V. Fiandalo, D. S. Watt and C. Liu, Org. Biomol. Chem., 2017, 15, 7623 DOI: 10.1039/C7OB01584D

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