Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma.
ABT-199/venetoclax
BH3-mimetics
MIK665/S64315
apoptosis
hepatocellular carcinoma (HCC)
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
08 Jun 2023
08 Jun 2023
Historique:
received:
06
05
2023
revised:
01
06
2023
accepted:
07
06
2023
medline:
28
6
2023
pubmed:
28
6
2023
entrez:
28
6
2023
Statut:
epublish
Résumé
Despite the recent approval of new therapies, the prognosis for patients with hepatocellular carcinoma (HCC) remains poor. There is a clinical need for new highly effective therapeutic options. Here, we present a combined application of BH3-mimetics as a potential new treatment option for HCC. BH3-mimetics inhibit anti-apoptotic proteins of the BCL-2 family and, thus, trigger the intrinsic apoptosis pathway. Anti-apoptotic BCL-2 proteins such as Bcl-2 and Mcl-1 are frequently overexpressed in HCC. Therefore, we analyzed the efficacy of the two BH3-mimetics ABT-199 (Bcl-2 inhibitor) and MIK665 (Mcl-1 inhibitor) in HCC cell lines with differential expression levels of endogenous Bcl-2 and Mcl-1. While administration of one BH3-mimetic alone did not substantially trigger cell death, the combination of two inhibitors enhanced induction of the intrinsic apoptosis pathway. Both drugs acted synergistically, highlighting the effectivity of this specific BH3-mimetic combination, particularly in HCC cell lines. These results indicate the potential of combining inhibitors of the BCL-2 family as new therapeutic options in HCC.
Identifiants
pubmed: 37371761
pii: biomedicines11061666
doi: 10.3390/biomedicines11061666
pmc: PMC10295989
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Wilhelm Sander Stiftung
ID : 2022.096.1
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