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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

Gamage, Chathurika D B ; Kim, Jeong-Hyeon ; Yang, Yi ; Taş, İsa LU orcid ; Park, So-Yeon ; Zhou, Rui ; Pulat, Sultan ; Varlı, Mücahit ; Hur, Jae-Seoun and Nam, Sang-Jip , et al. (2023) In Cancers 15(2).
Abstract

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), isolated from crude extracts of the endolichenic fungus from Pseudoplectania sp. (EL000327) and investigated the mechanism of action. CRC cells treated by B were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that B induced CRC cell death via multiple mechanisms including G2/M phase arrest caused by microtubule stabilization and... (More)

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), isolated from crude extracts of the endolichenic fungus from Pseudoplectania sp. (EL000327) and investigated the mechanism of action. CRC cells treated by B were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that 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 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 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 may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.

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publishing date
type
Contribution to journal
publication status
published
in
Cancers
volume
15
issue
2
article number
489
publisher
MDPI AG
external identifiers
  • scopus:85146600686
  • pmid:36672439
ISSN
2072-6694
DOI
10.3390/cancers15020489
language
English
LU publication?
no
id
b9ceeb24-cee2-4c4c-a4f3-ba19b51a0d80
date added to LUP
2026-09-23 15:57:49
date last changed
2026-10-09 03:01:12
@article{b9ceeb24-cee2-4c4c-a4f3-ba19b51a0d80,
  abstract     = {{<p>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), isolated from crude extracts of the endolichenic fungus from Pseudoplectania sp. (EL000327) and investigated the mechanism of action. CRC cells treated by B were subjected to apoptosis detection assays, immunofluorescence imaging, and molecular analyses such as immunoblotting and QRT-PCR. Our findings revealed that 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 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 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 may be a potential anticancer therapeutic against CRC that is suitable for clinical applications.</p>}},
  author       = {{Gamage, Chathurika D B and Kim, Jeong-Hyeon and Yang, Yi and Taş, İsa and Park, So-Yeon and Zhou, Rui and Pulat, Sultan and Varlı, Mücahit and Hur, Jae-Seoun and Nam, Sang-Jip and Kim, Hangun}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  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}},
  url          = {{http://dx.doi.org/10.3390/cancers15020489}},
  doi          = {{10.3390/cancers15020489}},
  volume       = {{15}},
  year         = {{2023}},
}