An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices
Histone deacetylase 8 (HDAC8) has been used as a therapeutic target for many cancers as it is highly expressed in neuroblastoma cells and breast cancer cells. HDAC8-selective fluorescent probes need to be urgently developed. Herein, two novel fluorescent probes, namely NP-C6-PCI and AM-C6-PCI , base...
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| Veröffentlicht in: | Organic & biomolecular chemistry 2021-10, Vol.19 (38), p.8352-8366 |
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| creator | Yan, Yinyu Huang, Chaoqun Shu, Yi Wen, Hongmei Shan, Chenxiao Wang, Xinzhi Liu, Jian Li, Wei |
| description | Histone deacetylase 8 (HDAC8) has been used as a therapeutic target for many cancers as it is highly expressed in neuroblastoma cells and breast cancer cells. HDAC8-selective fluorescent probes need to be urgently developed. Herein, two novel fluorescent probes, namely
NP-C6-PCI
and
AM-C6-PCI
, based on the conjugation of 1,8-naphthalimide with a highly selective inhibitor of HDAC8 (
PCI-34051
) were reported. Compared with
PCI-34051
(
K
D
= 6.25 × 10
−5
M),
NP-C6-PCI
(
K
D
= 8.05 × 10
−6
M) and
AM-C6-PCI
(
K
D
= 7.42 × 10
−6
M) showed great selectivity toward HDAC8. Two fluorescent probes exhibited high fluorescence intensity under
λ
ex
= 450 nm and a large Stokes shift (100 nm).
NP-C6-PCI
was selected for cell and tissue imaging due to the similarity in the bioactivity of
NP-C6-PCI
with
PCI-34051
. The ability of
NP-C6-PCI
to target imaging HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells was demonstrated. Furthermore,
NP-C6-PCI
was applied to imaging SH-SY5Y tumor tissue slices to indicate the relative expression level of HDAC8. Therefore, this HDAC8-selective fluorescent probe can be expected for applications in HDAC8-targeted drug screening as well as in pathologic diagnoses.
The fluorescence intensity of the HDAC8-selective fluorescence probe correlated well with the level of HDAC8 expression in living tumor cells and tissue slices. |
| doi_str_mv | 10.1039/d1ob01367j |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1039_D1OB01367J</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2573441732</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-c7f48c16339c1f9eab70a37d831a69a04301630588561e10a18117a6208075d73</originalsourceid><addsrcrecordid>eNpdkUFLw0AQhRdRrFYv3pUFLyJEZ7JJdnOsrVql0IseJWw2m7IlTepuUvDfu7G1gqd5vPkYHm8IuUC4Q2DpfYFNDsgSvjwgJxhxHkDM0sO9DmFATp1bAmDKk-iYDFgUh8JDJ-RjVNPpZDQWgdOVVq3ZaFpWXWO1U7pu6do2uXcaS81KLky9oKamldn0qu1W3le6qrxTa0dlXdDWONdp6iqjtDsjR6WsnD7fzSF5f3p8G0-D2fz5ZTyaBYox3gaKl5FQmDCWKixTLXMOkvFCMJRJKiFi4JcQCxEnqBEkCkQukxAE8LjgbEhutnd93M9OuzZbGdcHk7VuOpeFMWdRhJyFHr3-hy6bztY-XU-lLIUkAk_dbillG-esLrO19QXYrwwh60vPJjh_-Cn91cNXu5NdvtLFHv1t2QOXW8A6td_-fY19Axl2g6E</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2579390640</pqid></control><display><type>article</type><title>An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices</title><source>MEDLINE</source><source>Royal Society Of Chemistry Journals 2008-</source><source>Alma/SFX Local Collection</source><creator>Yan, Yinyu ; Huang, Chaoqun ; Shu, Yi ; Wen, Hongmei ; Shan, Chenxiao ; Wang, Xinzhi ; Liu, Jian ; Li, Wei</creator><creatorcontrib>Yan, Yinyu ; Huang, Chaoqun ; Shu, Yi ; Wen, Hongmei ; Shan, Chenxiao ; Wang, Xinzhi ; Liu, Jian ; Li, Wei</creatorcontrib><description>Histone deacetylase 8 (HDAC8) has been used as a therapeutic target for many cancers as it is highly expressed in neuroblastoma cells and breast cancer cells. HDAC8-selective fluorescent probes need to be urgently developed. Herein, two novel fluorescent probes, namely
NP-C6-PCI
and
AM-C6-PCI
, based on the conjugation of 1,8-naphthalimide with a highly selective inhibitor of HDAC8 (
PCI-34051
) were reported. Compared with
PCI-34051
(
K
D
= 6.25 × 10
−5
M),
NP-C6-PCI
(
K
D
= 8.05 × 10
−6
M) and
AM-C6-PCI
(
K
D
= 7.42 × 10
−6
M) showed great selectivity toward HDAC8. Two fluorescent probes exhibited high fluorescence intensity under
λ
ex
= 450 nm and a large Stokes shift (100 nm).
NP-C6-PCI
was selected for cell and tissue imaging due to the similarity in the bioactivity of
NP-C6-PCI
with
PCI-34051
. The ability of
NP-C6-PCI
to target imaging HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells was demonstrated. Furthermore,
NP-C6-PCI
was applied to imaging SH-SY5Y tumor tissue slices to indicate the relative expression level of HDAC8. Therefore, this HDAC8-selective fluorescent probe can be expected for applications in HDAC8-targeted drug screening as well as in pathologic diagnoses.
The fluorescence intensity of the HDAC8-selective fluorescence probe correlated well with the level of HDAC8 expression in living tumor cells and tissue slices.</description><identifier>ISSN: 1477-0520</identifier><identifier>ISSN: 1477-0539</identifier><identifier>EISSN: 1477-0539</identifier><identifier>DOI: 10.1039/d1ob01367j</identifier><identifier>PMID: 34528053</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Animals ; Biological activity ; Breast cancer ; Cell Line, Tumor ; Conjugation ; Drug screening ; Fluorescence ; Fluorescent Dyes - chemical synthesis ; Fluorescent Dyes - chemistry ; Fluorescent indicators ; Histone deacetylase ; Histone Deacetylase Inhibitors - chemical synthesis ; Histone Deacetylase Inhibitors - chemistry ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylases - metabolism ; Humans ; Hydroxamic Acids ; Imaging ; Indoles ; Mice ; Molecular Structure ; Naphthalimides - chemical synthesis ; Naphthalimides - chemistry ; Naphthalimides - pharmacology ; Neuroblastoma ; Neuroblastoma cells ; Optical Imaging ; Probes ; Repressor Proteins - antagonists & inhibitors ; Repressor Proteins - metabolism ; Selectivity ; Tissues ; Tumor cell lines ; Tumor cells ; Tumors</subject><ispartof>Organic & biomolecular chemistry, 2021-10, Vol.19 (38), p.8352-8366</ispartof><rights>Copyright Royal Society of Chemistry 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-c7f48c16339c1f9eab70a37d831a69a04301630588561e10a18117a6208075d73</citedby><cites>FETCH-LOGICAL-c337t-c7f48c16339c1f9eab70a37d831a69a04301630588561e10a18117a6208075d73</cites><orcidid>0000-0002-5345-604X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34528053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Yinyu</creatorcontrib><creatorcontrib>Huang, Chaoqun</creatorcontrib><creatorcontrib>Shu, Yi</creatorcontrib><creatorcontrib>Wen, Hongmei</creatorcontrib><creatorcontrib>Shan, Chenxiao</creatorcontrib><creatorcontrib>Wang, Xinzhi</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><title>An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices</title><title>Organic & biomolecular chemistry</title><addtitle>Org Biomol Chem</addtitle><description>Histone deacetylase 8 (HDAC8) has been used as a therapeutic target for many cancers as it is highly expressed in neuroblastoma cells and breast cancer cells. HDAC8-selective fluorescent probes need to be urgently developed. Herein, two novel fluorescent probes, namely
NP-C6-PCI
and
AM-C6-PCI
, based on the conjugation of 1,8-naphthalimide with a highly selective inhibitor of HDAC8 (
PCI-34051
) were reported. Compared with
PCI-34051
(
K
D
= 6.25 × 10
−5
M),
NP-C6-PCI
(
K
D
= 8.05 × 10
−6
M) and
AM-C6-PCI
(
K
D
= 7.42 × 10
−6
M) showed great selectivity toward HDAC8. Two fluorescent probes exhibited high fluorescence intensity under
λ
ex
= 450 nm and a large Stokes shift (100 nm).
NP-C6-PCI
was selected for cell and tissue imaging due to the similarity in the bioactivity of
NP-C6-PCI
with
PCI-34051
. The ability of
NP-C6-PCI
to target imaging HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells was demonstrated. Furthermore,
NP-C6-PCI
was applied to imaging SH-SY5Y tumor tissue slices to indicate the relative expression level of HDAC8. Therefore, this HDAC8-selective fluorescent probe can be expected for applications in HDAC8-targeted drug screening as well as in pathologic diagnoses.
The fluorescence intensity of the HDAC8-selective fluorescence probe correlated well with the level of HDAC8 expression in living tumor cells and tissue slices.</description><subject>Animals</subject><subject>Biological activity</subject><subject>Breast cancer</subject><subject>Cell Line, Tumor</subject><subject>Conjugation</subject><subject>Drug screening</subject><subject>Fluorescence</subject><subject>Fluorescent Dyes - chemical synthesis</subject><subject>Fluorescent Dyes - chemistry</subject><subject>Fluorescent indicators</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylase Inhibitors - chemical synthesis</subject><subject>Histone Deacetylase Inhibitors - chemistry</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases - metabolism</subject><subject>Humans</subject><subject>Hydroxamic Acids</subject><subject>Imaging</subject><subject>Indoles</subject><subject>Mice</subject><subject>Molecular Structure</subject><subject>Naphthalimides - chemical synthesis</subject><subject>Naphthalimides - chemistry</subject><subject>Naphthalimides - pharmacology</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma cells</subject><subject>Optical Imaging</subject><subject>Probes</subject><subject>Repressor Proteins - antagonists & inhibitors</subject><subject>Repressor Proteins - metabolism</subject><subject>Selectivity</subject><subject>Tissues</subject><subject>Tumor cell lines</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1477-0520</issn><issn>1477-0539</issn><issn>1477-0539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFLw0AQhRdRrFYv3pUFLyJEZ7JJdnOsrVql0IseJWw2m7IlTepuUvDfu7G1gqd5vPkYHm8IuUC4Q2DpfYFNDsgSvjwgJxhxHkDM0sO9DmFATp1bAmDKk-iYDFgUh8JDJ-RjVNPpZDQWgdOVVq3ZaFpWXWO1U7pu6do2uXcaS81KLky9oKamldn0qu1W3le6qrxTa0dlXdDWONdp6iqjtDsjR6WsnD7fzSF5f3p8G0-D2fz5ZTyaBYox3gaKl5FQmDCWKixTLXMOkvFCMJRJKiFi4JcQCxEnqBEkCkQukxAE8LjgbEhutnd93M9OuzZbGdcHk7VuOpeFMWdRhJyFHr3-hy6bztY-XU-lLIUkAk_dbillG-esLrO19QXYrwwh60vPJjh_-Cn91cNXu5NdvtLFHv1t2QOXW8A6td_-fY19Axl2g6E</recordid><startdate>20211006</startdate><enddate>20211006</enddate><creator>Yan, Yinyu</creator><creator>Huang, Chaoqun</creator><creator>Shu, Yi</creator><creator>Wen, Hongmei</creator><creator>Shan, Chenxiao</creator><creator>Wang, Xinzhi</creator><creator>Liu, Jian</creator><creator>Li, Wei</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T7</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5345-604X</orcidid></search><sort><creationdate>20211006</creationdate><title>An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices</title><author>Yan, Yinyu ; Huang, Chaoqun ; Shu, Yi ; Wen, Hongmei ; Shan, Chenxiao ; Wang, Xinzhi ; Liu, Jian ; Li, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-c7f48c16339c1f9eab70a37d831a69a04301630588561e10a18117a6208075d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Biological activity</topic><topic>Breast cancer</topic><topic>Cell Line, Tumor</topic><topic>Conjugation</topic><topic>Drug screening</topic><topic>Fluorescence</topic><topic>Fluorescent Dyes - chemical synthesis</topic><topic>Fluorescent Dyes - chemistry</topic><topic>Fluorescent indicators</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylase Inhibitors - chemical synthesis</topic><topic>Histone Deacetylase Inhibitors - chemistry</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylases - metabolism</topic><topic>Humans</topic><topic>Hydroxamic Acids</topic><topic>Imaging</topic><topic>Indoles</topic><topic>Mice</topic><topic>Molecular Structure</topic><topic>Naphthalimides - chemical synthesis</topic><topic>Naphthalimides - chemistry</topic><topic>Naphthalimides - pharmacology</topic><topic>Neuroblastoma</topic><topic>Neuroblastoma cells</topic><topic>Optical Imaging</topic><topic>Probes</topic><topic>Repressor Proteins - antagonists & inhibitors</topic><topic>Repressor Proteins - metabolism</topic><topic>Selectivity</topic><topic>Tissues</topic><topic>Tumor cell lines</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yan, Yinyu</creatorcontrib><creatorcontrib>Huang, Chaoqun</creatorcontrib><creatorcontrib>Shu, Yi</creatorcontrib><creatorcontrib>Wen, Hongmei</creatorcontrib><creatorcontrib>Shan, Chenxiao</creatorcontrib><creatorcontrib>Wang, Xinzhi</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Organic & biomolecular chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yan, Yinyu</au><au>Huang, Chaoqun</au><au>Shu, Yi</au><au>Wen, Hongmei</au><au>Shan, Chenxiao</au><au>Wang, Xinzhi</au><au>Liu, Jian</au><au>Li, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices</atitle><jtitle>Organic & biomolecular chemistry</jtitle><addtitle>Org Biomol Chem</addtitle><date>2021-10-06</date><risdate>2021</risdate><volume>19</volume><issue>38</issue><spage>8352</spage><epage>8366</epage><pages>8352-8366</pages><issn>1477-0520</issn><issn>1477-0539</issn><eissn>1477-0539</eissn><abstract>Histone deacetylase 8 (HDAC8) has been used as a therapeutic target for many cancers as it is highly expressed in neuroblastoma cells and breast cancer cells. HDAC8-selective fluorescent probes need to be urgently developed. Herein, two novel fluorescent probes, namely
NP-C6-PCI
and
AM-C6-PCI
, based on the conjugation of 1,8-naphthalimide with a highly selective inhibitor of HDAC8 (
PCI-34051
) were reported. Compared with
PCI-34051
(
K
D
= 6.25 × 10
−5
M),
NP-C6-PCI
(
K
D
= 8.05 × 10
−6
M) and
AM-C6-PCI
(
K
D
= 7.42 × 10
−6
M) showed great selectivity toward HDAC8. Two fluorescent probes exhibited high fluorescence intensity under
λ
ex
= 450 nm and a large Stokes shift (100 nm).
NP-C6-PCI
was selected for cell and tissue imaging due to the similarity in the bioactivity of
NP-C6-PCI
with
PCI-34051
. The ability of
NP-C6-PCI
to target imaging HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells was demonstrated. Furthermore,
NP-C6-PCI
was applied to imaging SH-SY5Y tumor tissue slices to indicate the relative expression level of HDAC8. Therefore, this HDAC8-selective fluorescent probe can be expected for applications in HDAC8-targeted drug screening as well as in pathologic diagnoses.
The fluorescence intensity of the HDAC8-selective fluorescence probe correlated well with the level of HDAC8 expression in living tumor cells and tissue slices.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>34528053</pmid><doi>10.1039/d1ob01367j</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-5345-604X</orcidid></addata></record> |
| fulltext | fulltext |
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| language | eng |
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| source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Animals Biological activity Breast cancer Cell Line, Tumor Conjugation Drug screening Fluorescence Fluorescent Dyes - chemical synthesis Fluorescent Dyes - chemistry Fluorescent indicators Histone deacetylase Histone Deacetylase Inhibitors - chemical synthesis Histone Deacetylase Inhibitors - chemistry Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases - metabolism Humans Hydroxamic Acids Imaging Indoles Mice Molecular Structure Naphthalimides - chemical synthesis Naphthalimides - chemistry Naphthalimides - pharmacology Neuroblastoma Neuroblastoma cells Optical Imaging Probes Repressor Proteins - antagonists & inhibitors Repressor Proteins - metabolism Selectivity Tissues Tumor cell lines Tumor cells Tumors |
| title | An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices |
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