8-Br-cGMP activates HSPB6 and increases the antineoplastic activity of quinidine in prostate cancer.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
19 Feb 2024
19 Feb 2024
Historique:
received:
23
09
2023
accepted:
06
02
2024
revised:
31
01
2024
medline:
20
2
2024
pubmed:
20
2
2024
entrez:
19
2
2024
Statut:
epublish
Résumé
Heat shock protein family B [small] member 6 (HSPB6), widely found in various muscles, has been recently identified as a tumor suppressor gene. However, its role in prostate cancer remains unexplored. Herein, we investigated the expression of HSPB6 in prostate cancer and its association with prognosis. Our findings revealed that HSPB6 downregulation in prostate cancer correlated with a poor prognosis. Moreover, we discovered that HSPB6 can be phosphorylated and activated by 8-Br-cGMP, leading to apoptosis in prostate cancer cells by activating Cofilin. Additionally, we demonstrated that knocking down E2F1 by quinidine administration enhances the transcriptional level of HSPB6. Furthermore, we evaluated the combination of quinidine and 8-Br-cGMP as a potential therapeutic strategy for prostate cancer. Our results revealed that the combined treatment was more effective than either treatment alone in inhibiting the growth of prostate cancer through the HSPB6 pathway, both in vitro and in vivo. Overall, our study provides compelling evidence that HSPB6 suppresses malignant behavior in prostate cancer by inducing apoptosis. The combination of quinidine and 8-Br-cGMP emerges as a promising approach for the treatment of prostate cancer.
Identifiants
pubmed: 38374143
doi: 10.1038/s41420-024-01853-3
pii: 10.1038/s41420-024-01853-3
doi:
Types de publication
Journal Article
Langues
eng
Pagination
90Informations de copyright
© 2024. The Author(s).
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