Libertellenone T, a Novel Compound Isolated from Endolichenic Fungus, Induces G2/M Phase Arrest, Apoptosis, and Autophagy by Activating the ROS/JNK Pathway in Colorectal Cancer Cells
Colorectal cancer (CRC) is the third most deadly type of cancer in the world and continuous investigations are required to discover novel therapeutics for CRC. Induction of apoptosis is one of the promising strategies to inhibit cancers. Here, we have identified a novel compound, Libertellenone T (...
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| Veröffentlicht in: | Cancers 2023-01, Vol.15 (2), p.489 |
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| creator | Gamage, Chathurika D B Kim, Jeong-Hyeon Yang, Yi Taş, İsa Park, So-Yeon Zhou, Rui Pulat, Sultan Varlı, Mücahit Hur, Jae-Seoun Nam, Sang-Jip Kim, Hangun |
| description | Colorectal cancer (CRC) is the third most deadly type of cancer in the world and continuous investigations are required to discover novel therapeutics for CRC. Induction of apoptosis is one of the promising strategies to inhibit cancers. Here, we have identified a novel compound, Libertellenone T (
), isolated from crude extracts of the endolichenic fungus from
sp. (EL000327) and investigated the mechanism of action. CRC cells treated by
were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that
induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that
induced the generation of reactive oxygen species (ROS) attributed to activating the JNK signaling pathway by which apoptosis and autophagy was induced in Caco2 cells. Moreover,
exhibited good synergistic effects when combined with the well-known anticancer drug, 5-FU, and another cytotoxic novel compound D, which was isolated from the same crude extract of EL000327. Overall, Libertellenone T induces G2/M phase arrest, apoptosis, and autophagy via activating the ROS/JNK pathway in CRC. Thus,
may be a potential anticancer therapeutic against CRC that is suitable for clinical applications. |
| doi_str_mv | 10.3390/cancers15020489 |
| format | Article |
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), isolated from crude extracts of the endolichenic fungus from
sp. (EL000327) and investigated the mechanism of action. CRC cells treated by
were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that
induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that
induced the generation of reactive oxygen species (ROS) attributed to activating the JNK signaling pathway by which apoptosis and autophagy was induced in Caco2 cells. Moreover,
exhibited good synergistic effects when combined with the well-known anticancer drug, 5-FU, and another cytotoxic novel compound D, which was isolated from the same crude extract of EL000327. Overall, Libertellenone T induces G2/M phase arrest, apoptosis, and autophagy via activating the ROS/JNK pathway in CRC. Thus,
may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15020489</identifier><identifier>PMID: 36672439</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antitumor agents ; Apoptosis ; Autophagy ; Cancer ; Caspase ; Cell cycle ; Cell death ; Cell growth ; Colorectal cancer ; Colorectal carcinoma ; Cytotoxicity ; Fungi ; Immunoblotting ; Immunofluorescence ; Kinases ; Metabolites ; Molecular modelling ; Mutation ; Natural products ; Reactive oxygen species ; Secondary metabolites ; Signal transduction</subject><ispartof>Cancers, 2023-01, Vol.15 (2), p.489</ispartof><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-a7d1969cfadd1258c99440a9c3d069af435b43a3599f51bbf2a03c77908ab2b23</citedby><cites>FETCH-LOGICAL-c421t-a7d1969cfadd1258c99440a9c3d069af435b43a3599f51bbf2a03c77908ab2b23</cites><orcidid>0000-0001-9871-8296 ; 0000-0001-6175-4015 ; 0000-0001-9241-7038 ; 0000-0001-8547-7075 ; 0000-0001-5889-8907 ; 0000-0001-5306-8584 ; 0000-0001-6663-8160</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857212/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857212/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36672439$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gamage, Chathurika D B</creatorcontrib><creatorcontrib>Kim, Jeong-Hyeon</creatorcontrib><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Taş, İsa</creatorcontrib><creatorcontrib>Park, So-Yeon</creatorcontrib><creatorcontrib>Zhou, Rui</creatorcontrib><creatorcontrib>Pulat, Sultan</creatorcontrib><creatorcontrib>Varlı, Mücahit</creatorcontrib><creatorcontrib>Hur, Jae-Seoun</creatorcontrib><creatorcontrib>Nam, Sang-Jip</creatorcontrib><creatorcontrib>Kim, Hangun</creatorcontrib><title>Libertellenone T, a Novel Compound Isolated from Endolichenic Fungus, Induces G2/M Phase Arrest, Apoptosis, and Autophagy by Activating the ROS/JNK Pathway in Colorectal Cancer Cells</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Colorectal cancer (CRC) is the third most deadly type of cancer in the world and continuous investigations are required to discover novel therapeutics for CRC. Induction of apoptosis is one of the promising strategies to inhibit cancers. Here, we have identified a novel compound, Libertellenone T (
), isolated from crude extracts of the endolichenic fungus from
sp. (EL000327) and investigated the mechanism of action. CRC cells treated by
were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that
induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that
induced the generation of reactive oxygen species (ROS) attributed to activating the JNK signaling pathway by which apoptosis and autophagy was induced in Caco2 cells. Moreover,
exhibited good synergistic effects when combined with the well-known anticancer drug, 5-FU, and another cytotoxic novel compound D, which was isolated from the same crude extract of EL000327. Overall, Libertellenone T induces G2/M phase arrest, apoptosis, and autophagy via activating the ROS/JNK pathway in CRC. Thus,
may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.</description><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Cancer</subject><subject>Caspase</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell growth</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Cytotoxicity</subject><subject>Fungi</subject><subject>Immunoblotting</subject><subject>Immunofluorescence</subject><subject>Kinases</subject><subject>Metabolites</subject><subject>Molecular modelling</subject><subject>Mutation</subject><subject>Natural products</subject><subject>Reactive oxygen species</subject><subject>Secondary metabolites</subject><subject>Signal transduction</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkkFv1DAQhSMEolXpmRsaiQuHXdaxkzi-IK1WbVlY2grKOZo4zsZVYqe2s2j_GL8PLy1VqS9jyd88vWe9JHmbko-MCbKQaKRyPs0JJVkpXiTHlHA6LwqRvXxyP0pOvb8l8TCW8oK_To5YUXCaMXGc_N7oWrmg-l4ZaxTczADh0u5UDys7jHYyDay97TGoBlpnBzgzje217JTREs4ns538DNammaTycEEX3-C6Q69g6ZzyYQbL0Y7Beh0pjGLLKdixw-0e6j0sZdA7DNpsIXQKvl_9WHy5_ArXGLpfuAdtooneOiUDRj9_48IqevVvklct9l6dPsyT5Of52c3q83xzdbFeLTdzmdE0zJE3qSiEbLFpUpqXUogsIygka0ghsM1YXmcMWS5Em6d13VIkTHIuSIk1rSk7ST7d645TPahGKhMc9tXo9IBuX1nU1f8vRnfV1u4qUeacpgeBDw8Czt5N8UOqQXsZI6BRdvIV5UVJqeA8j-j7Z-itnZyJ8Q4UT8syK0ikFveUdNZ7p9pHMympDrWontUibrx7muGR_1cC9gcRTrYa</recordid><startdate>20230112</startdate><enddate>20230112</enddate><creator>Gamage, Chathurika D B</creator><creator>Kim, Jeong-Hyeon</creator><creator>Yang, Yi</creator><creator>Taş, İsa</creator><creator>Park, So-Yeon</creator><creator>Zhou, Rui</creator><creator>Pulat, Sultan</creator><creator>Varlı, Mücahit</creator><creator>Hur, Jae-Seoun</creator><creator>Nam, Sang-Jip</creator><creator>Kim, Hangun</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9871-8296</orcidid><orcidid>https://orcid.org/0000-0001-6175-4015</orcidid><orcidid>https://orcid.org/0000-0001-9241-7038</orcidid><orcidid>https://orcid.org/0000-0001-8547-7075</orcidid><orcidid>https://orcid.org/0000-0001-5889-8907</orcidid><orcidid>https://orcid.org/0000-0001-5306-8584</orcidid><orcidid>https://orcid.org/0000-0001-6663-8160</orcidid></search><sort><creationdate>20230112</creationdate><title>Libertellenone T, a Novel Compound Isolated from Endolichenic Fungus, Induces G2/M Phase Arrest, Apoptosis, and Autophagy by Activating the ROS/JNK Pathway in Colorectal Cancer Cells</title><author>Gamage, Chathurika D B ; 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Induction of apoptosis is one of the promising strategies to inhibit cancers. Here, we have identified a novel compound, Libertellenone T (
), isolated from crude extracts of the endolichenic fungus from
sp. (EL000327) and investigated the mechanism of action. CRC cells treated by
were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that
induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that
induced the generation of reactive oxygen species (ROS) attributed to activating the JNK signaling pathway by which apoptosis and autophagy was induced in Caco2 cells. Moreover,
exhibited good synergistic effects when combined with the well-known anticancer drug, 5-FU, and another cytotoxic novel compound D, which was isolated from the same crude extract of EL000327. Overall, Libertellenone T induces G2/M phase arrest, apoptosis, and autophagy via activating the ROS/JNK pathway in CRC. Thus,
may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36672439</pmid><doi>10.3390/cancers15020489</doi><orcidid>https://orcid.org/0000-0001-9871-8296</orcidid><orcidid>https://orcid.org/0000-0001-6175-4015</orcidid><orcidid>https://orcid.org/0000-0001-9241-7038</orcidid><orcidid>https://orcid.org/0000-0001-8547-7075</orcidid><orcidid>https://orcid.org/0000-0001-5889-8907</orcidid><orcidid>https://orcid.org/0000-0001-5306-8584</orcidid><orcidid>https://orcid.org/0000-0001-6663-8160</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancers, 2023-01, Vol.15 (2), p.489 |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Antitumor agents Apoptosis Autophagy Cancer Caspase Cell cycle Cell death Cell growth Colorectal cancer Colorectal carcinoma Cytotoxicity Fungi Immunoblotting Immunofluorescence Kinases Metabolites Molecular modelling Mutation Natural products Reactive oxygen species Secondary metabolites Signal transduction |
| title | Libertellenone T, a Novel Compound Isolated from Endolichenic Fungus, Induces G2/M Phase Arrest, Apoptosis, and Autophagy by Activating the ROS/JNK Pathway in Colorectal Cancer Cells |
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