Mitochondrial dysfunction induced by callyspongiolide promotes autophagy-dependent cell death

Soohyun Lee, Yoonjeong Jeong, Jae Seok Roe, Hoyoung Huh, Sang Hoon Paik, Jaewhan Song

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Callyspongiolide is a marine macrolide known to induce caspaseindependent cancer cell death. While its toxic effects have been known, the mechanism leading to cell death is yet to be identified. We report that Callyspongiolide R form at C-21 (cally2R) causes mitochondrial dysfunction by inhibiting mitochondrial complex I or II, leading to a disruption of mitochondrial membrane potential and a deprivation of cellular energy. Subsequently, we observed, using electron microscopy, a drastic formation of autophagosome and mitophagy. Supporting these data, LC3, an autophagosome marker, was shown to co-localize with LAMP2, a lysosomal protein, showing autolysosome formation. RNA sequencing results indicated the induction of hypoxia and blocking of EGF-dependent pathways, which could be caused by induction of autophagy. Furthermore, mTOR and AKT pathways preventing autophagy were repressed while AMPK was upregulated, supporting autophagosome progress. Finally, the combination of cally2R with known anti-cancer drugs, such as gefitinib, sorafenib, and rapamycin, led to synergistic cell death, implicating potential therapeutic applications of callyspongiolide for future treatments. [BMB Reports 2021; 54(4): 227-232]

Original languageEnglish
Pages (from-to)227-232
Number of pages6
JournalBMB reports
Volume54
Issue number4
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 by the The Korean Society for Biochemistry and Molecular Biology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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