Methuosis Contributes to Jaspine-B-Induced Cell Death
Bielsa, Núria (Institut de Química Avançada de Catalunya)
Casasampere, Mireia (Institut de Química Avançada de Catalunya)
Abad, José Luis (Institut de Química Avançada de Catalunya)
Enrich, Carlos (Universitat de Barcelona. Departament de Biomedicina)
Delgado, Antonio (Institut de Química Avançada de Catalunya)
Fabriàs, Gemma (Institut de Química Avançada de Catalunya)
Lizcano de Vega, José Miguel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Casas, Josefina (Institut de Química Avançada de Catalunya)

Date:	2022
Description:	15 pàg.
Abstract:	Methuosis is a type of programmed cell death in which the cytoplasm is occupied by fluid-filled vacuoles that originate from macropinosomes (cytoplasmic vacuolation). A few molecules have been reported to behave as methuosis inducers in cancer cell lines. Jaspine B (JB) is a natural anhydrous sphingolipid (SL) derivative reported to induce cytoplasmic vacuolation and cytotoxicity in several cancer cell lines. Here, we have investigated the mechanism and signalling pathways involved in the cytotoxicity induced by the natural sphingolipid Jaspine B (JB) in lung adenocarcinoma A549 cells, which harbor the G12S K-Ras mutant. The effect of JB on inducing cytoplasmic vacuolation and modifying cell viability was determined in A549 cells, as well as in mouse embryonic fibroblasts (MEF) lacking either the autophagy-related gene ATG5 or BAX/BAK genes. Apoptosis was analyzed by flow cytometry after annexin V/propidium iodide staining, in the presence and absence of z-VAD. Autophagy was monitored by LC3-II/GFP-LC3-II analysis, and autophagic flux experiments using protease inhibitors. Phase contrast, confocal, and transmission electron microscopy were used to monitor cytoplasmic vacuolation and the uptake of Lucifer yellow to assess macropinocyosis. We present evidence that cytoplasmic vacuolation and methuosis are involved in Jaspine B cytotoxicity over A549 cells and that activation of 5' AMP-activated protein kinase (AMPK) could be involved in Jaspine-B-induced vacuolation, independently of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 1 (PI3K/Akt/mTORC1) axis.
Grants:	Ministerio de Economía y Competitividad CTQ2017-85378-R Agencia Estatal de Investigación PID2019-107561RB-I00 Agencia Estatal de Investigación PID2020-113813RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Apoptosis ; Autophagy ; Cytoplasmic vacuolization ; Methuosis ; Sphingolipids ; Cell Survival ; Sphingosine/analogs & derivatives ; Phosphatidylinositol 3-Kinases ; Neoplasms ; Mechanistic Target of Rapamycin Complex 1 ; Cell Death ; Cell Line, Tumor ; Fibroblasts ; Sphingolipids/pharmacology ; Mice ; Endosomes ; SDG 3 - Good Health and Well-being
Published in:	International journal of molecular sciences, Vol. 23 Núm. 13 (2022) , p. 7257, ISSN 1422-0067

DOI: 10.3390/ijms23137257
PMID: 35806262

15 p, 3.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles