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

Mykhaylo S. Frasinyuk; Wen Zhang; Przemyslaw Wyrebek; Tianxin Yu; Xuehe Xu; Vitaliy M. Sviripa; Svitlana P. Bondarenko; Yanqi Xie; Huy X. Ngo; Andrew J. Morris; James L. Mohler; Michael V. Fiandalo; David S. Watt; Chunming Liu

doi:10.1039/c7ob01584d

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

Mykhaylo S. Frasinyuk, Wen Zhang, Przemyslaw Wyrebek, Tianxin Yu, Xuehe Xu, Vitaliy M. Sviripa, Svitlana P. Bondarenko, Yanqi Xie, Huy X. Ngo, Andrew J. Morris, James L. Mohler, Michael V. Fiandalo, David S. Watt, Chunming Liu

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English
Pages (from-to)	7623-7629
Number of pages	7
Journal	Organic and Biomolecular Chemistry
Volume	15
Issue number	36
DOIs	https://doi.org/10.1039/c7ob01584d
State	Published - 2017

Bibliographical note

Publisher Copyright:
© 2017 The Royal Society of Chemistry.

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1039/c7ob01584d

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Frasinyuk, M. S., Zhang, W., Wyrebek, P., Yu, T., Xu, X., Sviripa, V. M., Bondarenko, S. P., Xie, Y., Ngo, H. X., Morris, A. J., Mohler, J. L., Fiandalo, M. V., Watt, D. S., & Liu, C. (2017). Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4). Organic and Biomolecular Chemistry, 15(36), 7623-7629. https://doi.org/10.1039/c7ob01584d

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title = "Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)",

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.",

author = "Frasinyuk, {Mykhaylo S.} and Wen Zhang and Przemyslaw Wyrebek and Tianxin Yu and Xuehe Xu and Sviripa, {Vitaliy M.} and Bondarenko, {Svitlana P.} and Yanqi Xie and Ngo, {Huy X.} and Morris, {Andrew J.} and Mohler, {James L.} and Fiandalo, {Michael V.} and Watt, {David S.} and Chunming Liu",

note = "Publisher Copyright: {\textcopyright} 2017 The Royal Society of Chemistry.",

year = "2017",

doi = "10.1039/c7ob01584d",

language = "English",

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pages = "7623--7629",

number = "36",

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Frasinyuk, MS, Zhang, W, Wyrebek, P, Yu, T, Xu, X, Sviripa, VM, Bondarenko, SP, Xie, Y, Ngo, HX, Morris, AJ, Mohler, JL, Fiandalo, MV, Watt, DS & Liu, C 2017, 'Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)', Organic and Biomolecular Chemistry, vol. 15, no. 36, pp. 7623-7629. https://doi.org/10.1039/c7ob01584d

Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4). / Frasinyuk, Mykhaylo S.; Zhang, Wen; Wyrebek, Przemyslaw et al.
In: Organic and Biomolecular Chemistry, Vol. 15, No. 36, 2017, p. 7623-7629.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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T2 - Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)

AU - Frasinyuk, Mykhaylo S.

AU - Zhang, Wen

AU - Wyrebek, Przemyslaw

AU - Yu, Tianxin

AU - Xu, Xuehe

AU - Sviripa, Vitaliy M.

AU - Bondarenko, Svitlana P.

AU - Xie, Yanqi

AU - Ngo, Huy X.

AU - Morris, Andrew J.

AU - Mohler, James L.

AU - Fiandalo, Michael V.

AU - Watt, David S.

AU - Liu, Chunming

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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AN - SCOPUS:85029761843

SN - 1477-0520

VL - 15

SP - 7623

EP - 7629

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 36

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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