Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7
The Wnt/ β -catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/ β -catenin signaling pathway, named LPD-01 ( 1 ), and 1 inhibited the growth of hum...
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| Veröffentlicht in: | Journal of natural medicines 2024-03, Vol.78 (2), p.370-381 |
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| container_title | Journal of natural medicines |
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| creator | Kitagawa, Takahiro Matsumoto, Takahiro Ohta, Tomoe Yoshida, Tatsusada Saito, Youhei Nakayama, Yuji Hadate, Yuki Ashihara, Eishi Watanabe, Tetsushi |
| description | The Wnt/
β
-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/
β
-catenin signaling pathway, named LPD-01 (
1
), and
1
inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that
1
inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of
1
in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/
β
-catenin signaling pathway
-
related proteins. As a result,
1
inhibited the expression of target proteins of Wnt/
β
-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (
β
-catenin) was not decreased, suggesting that
1
inhibited the Wnt/
β
-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of
1
using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that
1
directly binds to importin7. As expected,
1
inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-
β
-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/
β
-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of
1
for inhibition of the Wnt/
β
-catenin signaling pathway.
Graphical abstract |
| doi_str_mv | 10.1007/s11418-023-01774-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2918197221</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2918197221</sourcerecordid><originalsourceid>FETCH-LOGICAL-c326t-58b25307f36eeba8f0d1271a6b7c0d2f6d01898cdb17671a2164c544fff37e3c3</originalsourceid><addsrcrecordid>eNp9kD1v2zAQhomgQew4-QMdCgJduijh8WhSGouk-QAMxEMyExR1EhRYkktKg_596DhNgQ5dyMPxuffAh7GvIK5ACHMdARTkmZCYCTBGZfMJW0KuIbUK_JJqVCJDpXDBzmN8FUJJRDhjC8ylXmuQS7bdtH1Fwe3nMPTEXe92QzMR32xvUyh3kTvuXe8p8DGQGzvqR-6aw1nOfHShobHtG952-yGkylyw09rtIl1-3Cv2cvfr-eYh2zzdP9783GQepR6zdV7KNQpToyYqXV6LCqQBp0vjRSVrXQnIi9xXJRid-hK08mul6rpGQ-hxxX4cc_dh-D1RHG3XRk-7netpmKKVBeRQGCkhod__QV-HKaSfHihEoUAUIlHySPkwxBiotvvQdi7MFoQ9-LZH3zb5tu--7ZyGvn1ET2VH1efIH8EJwCMQ01PfUPi7-z-xbyH6ifc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2933041090</pqid></control><display><type>article</type><title>Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7</title><source>SpringerNature Journals</source><creator>Kitagawa, Takahiro ; Matsumoto, Takahiro ; Ohta, Tomoe ; Yoshida, Tatsusada ; Saito, Youhei ; Nakayama, Yuji ; Hadate, Yuki ; Ashihara, Eishi ; Watanabe, Tetsushi</creator><creatorcontrib>Kitagawa, Takahiro ; Matsumoto, Takahiro ; Ohta, Tomoe ; Yoshida, Tatsusada ; Saito, Youhei ; Nakayama, Yuji ; Hadate, Yuki ; Ashihara, Eishi ; Watanabe, Tetsushi</creatorcontrib><description>The Wnt/
β
-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/
β
-catenin signaling pathway, named LPD-01 (
1
), and
1
inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that
1
inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of
1
in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/
β
-catenin signaling pathway
-
related proteins. As a result,
1
inhibited the expression of target proteins of Wnt/
β
-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (
β
-catenin) was not decreased, suggesting that
1
inhibited the Wnt/
β
-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of
1
using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that
1
directly binds to importin7. As expected,
1
inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-
β
-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/
β
-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of
1
for inhibition of the Wnt/
β
-catenin signaling pathway.
Graphical abstract</description><identifier>ISSN: 1340-3443</identifier><identifier>EISSN: 1861-0293</identifier><identifier>DOI: 10.1007/s11418-023-01774-y</identifier><identifier>PMID: 38265612</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; c-Myc protein ; Cancer therapies ; Cell proliferation ; Colorectal cancer ; Colorectal carcinoma ; Complementary & Alternative Medicine ; Mass spectroscopy ; Medicinal Chemistry ; Myc protein ; Nuclear transport ; Original Paper ; Pharmacology/Toxicology ; Pharmacy ; Plant Sciences ; Proteins ; Signal transduction ; siRNA ; Smad2 protein ; Smad3 protein ; Survivin ; Transforming growth factor-b ; Wnt protein ; β-Catenin</subject><ispartof>Journal of natural medicines, 2024-03, Vol.78 (2), p.370-381</ispartof><rights>The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-58b25307f36eeba8f0d1271a6b7c0d2f6d01898cdb17671a2164c544fff37e3c3</cites><orcidid>0000-0003-2408-669X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11418-023-01774-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11418-023-01774-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38265612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kitagawa, Takahiro</creatorcontrib><creatorcontrib>Matsumoto, Takahiro</creatorcontrib><creatorcontrib>Ohta, Tomoe</creatorcontrib><creatorcontrib>Yoshida, Tatsusada</creatorcontrib><creatorcontrib>Saito, Youhei</creatorcontrib><creatorcontrib>Nakayama, Yuji</creatorcontrib><creatorcontrib>Hadate, Yuki</creatorcontrib><creatorcontrib>Ashihara, Eishi</creatorcontrib><creatorcontrib>Watanabe, Tetsushi</creatorcontrib><title>Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7</title><title>Journal of natural medicines</title><addtitle>J Nat Med</addtitle><addtitle>J Nat Med</addtitle><description>The Wnt/
β
-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/
β
-catenin signaling pathway, named LPD-01 (
1
), and
1
inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that
1
inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of
1
in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/
β
-catenin signaling pathway
-
related proteins. As a result,
1
inhibited the expression of target proteins of Wnt/
β
-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (
β
-catenin) was not decreased, suggesting that
1
inhibited the Wnt/
β
-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of
1
using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that
1
directly binds to importin7. As expected,
1
inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-
β
-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/
β
-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of
1
for inhibition of the Wnt/
β
-catenin signaling pathway.
Graphical abstract</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>c-Myc protein</subject><subject>Cancer therapies</subject><subject>Cell proliferation</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Complementary & Alternative Medicine</subject><subject>Mass spectroscopy</subject><subject>Medicinal Chemistry</subject><subject>Myc protein</subject><subject>Nuclear transport</subject><subject>Original Paper</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Plant Sciences</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>siRNA</subject><subject>Smad2 protein</subject><subject>Smad3 protein</subject><subject>Survivin</subject><subject>Transforming growth factor-b</subject><subject>Wnt protein</subject><subject>β-Catenin</subject><issn>1340-3443</issn><issn>1861-0293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kD1v2zAQhomgQew4-QMdCgJduijh8WhSGouk-QAMxEMyExR1EhRYkktKg_596DhNgQ5dyMPxuffAh7GvIK5ACHMdARTkmZCYCTBGZfMJW0KuIbUK_JJqVCJDpXDBzmN8FUJJRDhjC8ylXmuQS7bdtH1Fwe3nMPTEXe92QzMR32xvUyh3kTvuXe8p8DGQGzvqR-6aw1nOfHShobHtG952-yGkylyw09rtIl1-3Cv2cvfr-eYh2zzdP9783GQepR6zdV7KNQpToyYqXV6LCqQBp0vjRSVrXQnIi9xXJRid-hK08mul6rpGQ-hxxX4cc_dh-D1RHG3XRk-7netpmKKVBeRQGCkhod__QV-HKaSfHihEoUAUIlHySPkwxBiotvvQdi7MFoQ9-LZH3zb5tu--7ZyGvn1ET2VH1efIH8EJwCMQ01PfUPi7-z-xbyH6ifc</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Kitagawa, Takahiro</creator><creator>Matsumoto, Takahiro</creator><creator>Ohta, Tomoe</creator><creator>Yoshida, Tatsusada</creator><creator>Saito, Youhei</creator><creator>Nakayama, Yuji</creator><creator>Hadate, Yuki</creator><creator>Ashihara, Eishi</creator><creator>Watanabe, Tetsushi</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2408-669X</orcidid></search><sort><creationdate>20240301</creationdate><title>Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7</title><author>Kitagawa, Takahiro ; Matsumoto, Takahiro ; Ohta, Tomoe ; Yoshida, Tatsusada ; Saito, Youhei ; Nakayama, Yuji ; Hadate, Yuki ; Ashihara, Eishi ; Watanabe, Tetsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-58b25307f36eeba8f0d1271a6b7c0d2f6d01898cdb17671a2164c544fff37e3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>c-Myc protein</topic><topic>Cancer therapies</topic><topic>Cell proliferation</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Complementary & Alternative Medicine</topic><topic>Mass spectroscopy</topic><topic>Medicinal Chemistry</topic><topic>Myc protein</topic><topic>Nuclear transport</topic><topic>Original Paper</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Plant Sciences</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>siRNA</topic><topic>Smad2 protein</topic><topic>Smad3 protein</topic><topic>Survivin</topic><topic>Transforming growth factor-b</topic><topic>Wnt protein</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kitagawa, Takahiro</creatorcontrib><creatorcontrib>Matsumoto, Takahiro</creatorcontrib><creatorcontrib>Ohta, Tomoe</creatorcontrib><creatorcontrib>Yoshida, Tatsusada</creatorcontrib><creatorcontrib>Saito, Youhei</creatorcontrib><creatorcontrib>Nakayama, Yuji</creatorcontrib><creatorcontrib>Hadate, Yuki</creatorcontrib><creatorcontrib>Ashihara, Eishi</creatorcontrib><creatorcontrib>Watanabe, Tetsushi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of natural medicines</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kitagawa, Takahiro</au><au>Matsumoto, Takahiro</au><au>Ohta, Tomoe</au><au>Yoshida, Tatsusada</au><au>Saito, Youhei</au><au>Nakayama, Yuji</au><au>Hadate, Yuki</au><au>Ashihara, Eishi</au><au>Watanabe, Tetsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7</atitle><jtitle>Journal of natural medicines</jtitle><stitle>J Nat Med</stitle><addtitle>J Nat Med</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>78</volume><issue>2</issue><spage>370</spage><epage>381</epage><pages>370-381</pages><issn>1340-3443</issn><eissn>1861-0293</eissn><abstract>The Wnt/
β
-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/
β
-catenin signaling pathway, named LPD-01 (
1
), and
1
inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that
1
inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of
1
in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/
β
-catenin signaling pathway
-
related proteins. As a result,
1
inhibited the expression of target proteins of Wnt/
β
-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (
β
-catenin) was not decreased, suggesting that
1
inhibited the Wnt/
β
-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of
1
using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that
1
directly binds to importin7. As expected,
1
inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-
β
-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/
β
-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of
1
for inhibition of the Wnt/
β
-catenin signaling pathway.
Graphical abstract</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>38265612</pmid><doi>10.1007/s11418-023-01774-y</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-2408-669X</orcidid></addata></record> |
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| source | SpringerNature Journals |
| subjects | Biomedical and Life Sciences Biomedicine c-Myc protein Cancer therapies Cell proliferation Colorectal cancer Colorectal carcinoma Complementary & Alternative Medicine Mass spectroscopy Medicinal Chemistry Myc protein Nuclear transport Original Paper Pharmacology/Toxicology Pharmacy Plant Sciences Proteins Signal transduction siRNA Smad2 protein Smad3 protein Survivin Transforming growth factor-b Wnt protein β-Catenin |
| title | Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7 |
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