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

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 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.

Original languageEnglish
Article number489
JournalCancers
Volume15
Issue number2
DOIs
StatePublished - Jan 2023

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea grant (NRF-2020R1C1C1007832) funded by the Korean government (MSIP).

Publisher Copyright:
© 2023 by the authors.

Keywords

  • CRC
  • G2/M phase arrest
  • Libertellenone T
  • ROS/JNK signaling
  • apoptosis
  • autophagy

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