LNS8801 inhibits Acute Myeloid Leukemia by Inducing the Production of Reactive Oxygen Species and Activating the Endoplasmic Reticulum Stress Pathway.
Journal
Cancer research communications
ISSN: 2767-9764
Titre abrégé: Cancer Res Commun
Pays: United States
ID NLM: 9918281580506676
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
23
11
2022
revised:
24
03
2023
accepted:
17
07
2023
medline:
22
8
2023
pubmed:
21
8
2023
entrez:
21
8
2023
Statut:
epublish
Résumé
Despite recent therapeutic advances, the 5-year survival rate for adults with acute myeloid leukemia (AML) is poor and standard-of-care chemotherapy is associated with significant toxicity, highlighting the need for new therapeutic approaches. Recent work from our group and others established that the G protein-coupled estrogen receptor (GPER) is tumor suppressive in melanoma and other solid tumors. We performed a preliminary screen of human cancer cell lines from multiple malignancies and found that LNS8801, a synthetic pharmacologic agonist of GPER currently in early phase clinical trials, promoted apoptosis in human AML cells. Using human AML cell lines and primary cells, we show that LNS8801 inhibits human AML in preclinical Previous work demonstrated that LNS8801 inhibits cancer via GPER activation, especially in solid tumors. Here we show that LNS8801 inhibits AML via GPER-independent mechanisms that include ROS induction and ER activation.
Identifiants
pubmed: 37599786
doi: 10.1158/2767-9764.CRC-22-0478
pii: CRC-22-0478
pmc: PMC10438922
doi:
Substances chimiques
Reactive Oxygen Species
0
Endoribonucleases
EC 3.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Estrogens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1594-1606Subventions
Organisme : NCI NIH HHS
ID : K08 CA230190
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA163566
Pays : United States
Organisme : NCI NIH HHS
ID : R41 CA228695
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA265219
Pays : United States
Informations de copyright
© 2023 The Authors; Published by the American Association for Cancer Research.
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