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Enhancement of acetate-induced apoptosis of colorectal cancer cells by cathepsin D inhibition depends on oligomycin A-sensitive respiration

dc.contributor.authorAlves, Sara
dc.contributor.authorSantos-Pereira, Cátia
dc.contributor.authorOliveira, Cláudia S. F.
dc.contributor.authorPreto, Ana
dc.contributor.authorChaves, Susana R.
dc.contributor.authorCôrte-Real, Manuela
dc.date.accessioned2024-05-15T10:30:12Z
dc.date.available2024-05-15T10:30:12Z
dc.date.issued2024-04-12
dc.description.abstractColorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/biom14040473pt_PT
dc.identifier.eid85191318151
dc.identifier.issn2218-273X
dc.identifier.urihttp://hdl.handle.net/10400.14/45101
dc.identifier.wos001210268300001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectColorectal cancerpt_PT
dc.subjectShort-chain fatty acidspt_PT
dc.subjectAcetatept_PT
dc.subjectApoptosispt_PT
dc.subjectCathepsin Dpt_PT
dc.subjectCell respirationpt_PT
dc.titleEnhancement of acetate-induced apoptosis of colorectal cancer cells by cathepsin D inhibition depends on oligomycin A-sensitive respirationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage13pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleBiomoleculespt_PT
oaire.citation.volume14pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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