Histone deacetylase inhibitor 2-hexyl-4-pentynoic acid enhances hydroxyurea therapeutic effect in triple-negative breast cancer cells.

Ding, C; Su, B; Li, Q; Ding, W; Liu, G; Cai, Z; Zhang, F; Lim, D; Feng, Z

Histone deacetylase inhibitor 2-hexyl-4-pentynoic acid enhances hydroxyurea therapeutic effect in triple-negative breast cancer cells.

Ding, C Su, B Li, Q Ding, W Liu, G Cai, Z Zhang, F Lim, D Feng, Z

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Mutat Res Genet Toxicol Environ Mutagen, 2022, 873, pp. 503422
Issue Date:: 2022-01

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Field	Value	Language
dc.contributor.author	Ding, C
dc.contributor.author	Su, B
dc.contributor.author	Li, Q
dc.contributor.author	Ding, W
dc.contributor.author	Liu, G
dc.contributor.author	Cai, Z
dc.contributor.author	Zhang, F
dc.contributor.author	Lim, D
dc.contributor.author	Feng, Z
dc.date.accessioned	2023-07-17T04:51:31Z
dc.date.available	2021-11-03
dc.date.available	2023-07-17T04:51:31Z
dc.date.issued	2022-01
dc.identifier.citation	Mutat Res Genet Toxicol Environ Mutagen, 2022, 873, pp. 503422
dc.identifier.issn	1383-5718
dc.identifier.issn	1879-3592
dc.identifier.uri	http://hdl.handle.net/10453/171552
dc.description.abstract	Triple-negative breast cancer (TNBC) treatment has only limited effect, and it causes a significant number of deaths. Histone deacetylase inhibitors (HDACis) are emerging as promising anti-tumor agents in many types of cancers. We thus hypothesized that 2-hexyl-4-pentynoic acid (HPTA), a novel HDACi, could sensitize TNBC to hydroxyurea (HU, a ribonucleotide reductase inhibitor). In the present study, we investigated the effect of HPTA, alone or in combination with HU on cell survival, DNA double-strand breaks (DSBs), key homologous recombination (HR) repair proteins and cell cycle progression in MDA-MB-468 and MDA-MB-231 human TNBC cell lines. HPTA and HU synergistically inhibited the survival of TNBC cell lines and resulted in the accumulation of DNA double-strand breaks (DSBs). HPTA can sensitize TNBC cells to HU by inhibiting replication protein A2 (RPA2) hyperphosphorylation-mediated HR repair, and lessen cell accumulation in S-phase by inhibiting ATR-CHK1 signaling pathway. Taken together, our data suggested that HPTA enhances HU therapeutic effect by blocking the HR repair and regulating cell cycle progression in TNBC.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Mutat Res Genet Toxicol Environ Mutagen
dc.relation.isbasedon	10.1016/j.mrgentox.2021.503422
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1002 Environmental Biotechnology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Toxicology
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.subject.mesh	Cell Cycle
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	DNA Breaks, Double-Stranded
dc.subject.mesh	DNA Repair
dc.subject.mesh	Drug Synergism
dc.subject.mesh	Fatty Acids, Unsaturated
dc.subject.mesh	Histone Deacetylase Inhibitors
dc.subject.mesh	Humans
dc.subject.mesh	Hydroxyurea
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Humans
dc.subject.mesh	Hydroxyurea
dc.subject.mesh	Fatty Acids, Unsaturated
dc.subject.mesh	Cell Cycle
dc.subject.mesh	DNA Repair
dc.subject.mesh	Drug Synergism
dc.subject.mesh	DNA Breaks, Double-Stranded
dc.subject.mesh	Histone Deacetylase Inhibitors
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Cell Cycle
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	DNA Breaks, Double-Stranded
dc.subject.mesh	DNA Repair
dc.subject.mesh	Drug Synergism
dc.subject.mesh	Fatty Acids, Unsaturated
dc.subject.mesh	Histone Deacetylase Inhibitors
dc.subject.mesh	Humans
dc.subject.mesh	Hydroxyurea
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.title	Histone deacetylase inhibitor 2-hexyl-4-pentynoic acid enhances hydroxyurea therapeutic effect in triple-negative breast cancer cells.
dc.type	Journal Article
utslib.citation.volume	873
utslib.location.activity	Netherlands
utslib.for	1002 Environmental Biotechnology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	closed_access	*
dc.date.updated	2023-07-17T04:51:29Z
pubs.publication-status	Published
pubs.volume	873

Abstract:

Triple-negative breast cancer (TNBC) treatment has only limited effect, and it causes a significant number of deaths. Histone deacetylase inhibitors (HDACis) are emerging as promising anti-tumor agents in many types of cancers. We thus hypothesized that 2-hexyl-4-pentynoic acid (HPTA), a novel HDACi, could sensitize TNBC to hydroxyurea (HU, a ribonucleotide reductase inhibitor). In the present study, we investigated the effect of HPTA, alone or in combination with HU on cell survival, DNA double-strand breaks (DSBs), key homologous recombination (HR) repair proteins and cell cycle progression in MDA-MB-468 and MDA-MB-231 human TNBC cell lines. HPTA and HU synergistically inhibited the survival of TNBC cell lines and resulted in the accumulation of DNA double-strand breaks (DSBs). HPTA can sensitize TNBC cells to HU by inhibiting replication protein A2 (RPA2) hyperphosphorylation-mediated HR repair, and lessen cell accumulation in S-phase by inhibiting ATR-CHK1 signaling pathway. Taken together, our data suggested that HPTA enhances HU therapeutic effect by blocking the HR repair and regulating cell cycle progression in TNBC.

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http://hdl.handle.net/10453/171552