계명대학교 의학도서관 Repository

Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition

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Author(s)
Minho WonSunkyung ChoiSeonghye CheonEun-Mi KimTaeg Kyu KwonJaewhan KimYong-Eun KimKyung-Cheol SohnGang Min HurKee K. Kim
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Cell Biol Toxicol
Issued Date
2023
Volume
39
Issue
1
Keyword
Octyl syringateAutophagic fluxLysosomal dysfunctionNon-apoptotic cell deathLysosome target therapy
Abstract
The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1573-6822
Source
https://link.springer.com/article/10.1007/s10565-021-09653-6
DOI
10.1007/s10565-021-09653-6
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44932
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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