Everolimus and plicamycin specifically target chemoresistant colorectal cancer cells of the CMS4 subtype.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
21 10 2021
21 10 2021
Historique:
received:
11
06
2021
accepted:
05
10
2021
revised:
19
09
2021
entrez:
22
10
2021
pubmed:
23
10
2021
medline:
19
2
2022
Statut:
epublish
Résumé
Colorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.
Identifiants
pubmed: 34675191
doi: 10.1038/s41419-021-04270-x
pii: 10.1038/s41419-021-04270-x
pmc: PMC8531384
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
CD2-associated protein
0
Cytoskeletal Proteins
0
Everolimus
9HW64Q8G6G
Plicamycin
NIJ123W41V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
978Informations de copyright
© 2021. The Author(s).
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