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

Won, Minho; Choi, Sunkyung; Cheon, Seonghye; Kim, Eun‐Mi; Kwon, Taeg Kyu; Kim, Jaewhan; Kim, Yong-Eun; Sohn, Kyung-Ah; Hur, Gang Min; Kim, Kee K.

doi:10.1007/s10565-021-09653-6

Cited by 1 publication

(2 citation statements)

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“…Autophagy is a conserved process that plays a key role in maintaining the balance between cell death and survival 5,6 . Typical features of autophagic cell death include the accumulation of autophagic organelles such as autophagosomes and autolysomes 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Autophagy is a conserved process that plays a key role in maintaining the balance between cell death and survival. 5,6 Typical features of autophagic cell death include the accumulation of autophagic organelles such as autophagosomes and autolysomes. 7 Light chain 3-II (LC3-II) is an autophagy marker that plays a key role in the elongation of double membranes during induction of autophagic flux and is necessary for the formation of autophagosomes.…”

Section: Introductionmentioning

confidence: 99%

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Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer

Kong

Zhu

Zheng

et al. 2022

J Cellular Molecular Medi

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Larotrectinib (Lar) is a highly selective and potent small-molecule inhibitor used in patients with tropomyosin receptor kinase (TRK) fusion-positive cancers, including colon cancer. However, the underlying molecular mechanisms specifically in patients with colon cancer have not yet been explored. Our data showed that Lar significantly suppressed proliferation and migration of colon cancer cells. In addition, Lar suppressed the epithelial-mesenchymal transition (EMT) process, as evidenced by elevation in E-cadherin (E-cad), and downregulation of vimentin and matrix metalloproteinase (MMP) 2/9 expression. Furthermore, Lar was found to activate autophagic flux, in which Lar increased the ratio between LC3II/LC3I and decreased the expression of p62 in colon cancer cells. More importantly, Lar also increased AMPK phosphorylation and suppressed mTOR phosphorylation in colon cancer cells. However, when we silenced AMPK in colon cancer cells, Lar-induced accumulation of autolysomes as well as Lar-induced suppression of the EMT process were significantly diminished. An in vivo assay also confirmed that tumour volume and weight decreased in Lar-treated mice than in control mice. Taken together, this study suggests that Lar significantly suppresses colon cancer proliferation and migration by activating AMPK/mTORmediated autophagic cell death.

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Section: Introductionmentioning

confidence: 99%