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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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/2/489 |
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| author | Chathurika D. B. Gamage Jeong-Hyeon Kim Yi Yang İsa Taş So-Yeon Park Rui Zhou Sultan Pulat Mücahit Varlı Jae-Seoun Hur Sang-Jip Nam Hangun Kim |
| author_facet | Chathurika D. B. Gamage Jeong-Hyeon Kim Yi Yang İsa Taş So-Yeon Park Rui Zhou Sultan Pulat Mücahit Varlı Jae-Seoun Hur Sang-Jip Nam Hangun Kim |
| author_sort | Chathurika D. B. Gamage |
| collection | DOAJ |
| 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 (<b>B</b>), isolated from crude extracts of the endolichenic fungus from <i>Pseudoplectania</i> sp. (EL000327) and investigated the mechanism of action. CRC cells treated by <b>B</b> were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that <b>B</b> induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that <b>B</b> 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, <b>B</b> 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, <b>B</b> may be a potential anticancer therapeutic against CRC that is suitable for clinical applications. |
| first_indexed | 2024-03-09T13:17:06Z |
| format | Article |
| id | doaj.art-08db1c1be105402a932aacf15efde643 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:17:06Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-08db1c1be105402a932aacf15efde6432023-11-30T21:34:36ZengMDPI AGCancers2072-66942023-01-0115248910.3390/cancers15020489Libertellenone 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 CellsChathurika D. B. Gamage0Jeong-Hyeon Kim1Yi Yang2İsa Taş3So-Yeon Park4Rui Zhou5Sultan Pulat6Mücahit Varlı7Jae-Seoun Hur8Sang-Jip Nam9Hangun Kim10College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaDepartment of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaKorean Lichen Research Institute, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaDepartment of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of KoreaCollege of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Republic of KoreaColorectal 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 (<b>B</b>), isolated from crude extracts of the endolichenic fungus from <i>Pseudoplectania</i> sp. (EL000327) and investigated the mechanism of action. CRC cells treated by <b>B</b> were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that <b>B</b> induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and caspase-dependent apoptosis. Further studies revealed that <b>B</b> 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, <b>B</b> 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, <b>B</b> may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.https://www.mdpi.com/2072-6694/15/2/489CRCLibertellenone TG2/M phase arrestapoptosisautophagyROS/JNK signaling |
| spellingShingle | Chathurika D. B. Gamage Jeong-Hyeon Kim Yi Yang İsa Taş So-Yeon Park Rui Zhou Sultan Pulat Mücahit Varlı Jae-Seoun Hur Sang-Jip Nam Hangun Kim 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 Cancers CRC Libertellenone T G2/M phase arrest apoptosis autophagy ROS/JNK signaling |
| 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_full | 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_fullStr | 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_full_unstemmed | 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_short | 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_sort | 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 |
| topic | CRC Libertellenone T G2/M phase arrest apoptosis autophagy ROS/JNK signaling |
| url | https://www.mdpi.com/2072-6694/15/2/489 |
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