CAVPENET Peptide Inhibits Prostate Cancer Cells Proliferation and Migration through PP1γ-Dependent Inhibition of AKT Signaling
Matos, Bárbara and Gomes, Antoniel A. S. and Bernardino, Raquel and Alves, Marco G. and Howl, John and Jerónimo, Carmen and Fardilha, Margarida (2024) CAVPENET Peptide Inhibits Prostate Cancer Cells Proliferation and Migration through PP1γ-Dependent Inhibition of AKT Signaling. Pharmaceutics, 16 (9). pp. 1199-1225. ISSN 1999-4923
|
Text
pharmaceutics-16-01199.pdf - Published Version Available under License Creative Commons Attribution. Download (4MB) |
Abstract
Protein phosphatase 1 (PP1) complexes have emerged as promising targets for anticancer therapies. The ability of peptides to mimic PP1-docking motifs, and so modulate interactions with regulatory factors, has enabled the creation of highly selective modulators of PP1-dependent cellular processes that promote tumor growth. The major objective of this study was to develop a novel bioactive cell-penetrating peptide (bioportide), which, by mimicking the PP1-binding motif of caveolin-1 (CAV1), would regulate PP1 activity, to hinder prostate cancer (PCa) progression. The designed bioportide, herein designated CAVPENET, and a scrambled homologue, were synthesized using microwave-assisted solid-phase methodologies and evaluated using PCa cell lines. Our findings indicate that CAVPENET successfully entered PCa cells to influence both viability and migration. This tumor suppressor activity of CAVPENET was attributed to inhibition of AKT signaling, a consequence of increased PP1γ activity. This led to the suppression of glycolytic metabolism and alteration in lipid metabolism, collectively representing the primary mechanism responsible for the anticancer properties of CAVPENET. Our results underscore the potential of the designed peptide as a novel therapy for PCa patients, setting the stage for further testing in more advanced models to fully realize its therapeutic promise.
| Item Type: | Article | ||||||
|---|---|---|---|---|---|---|---|
| Identification Number: | https://doi.org/10.3390/pharmaceutics16091199 | ||||||
| Dates: |
|
||||||
| Uncontrolled Keywords: | prostate cancer, treatment, protein-protein interaction, protein phosphatase 1, PP1-targeting peptide | ||||||
| Subjects: | CAH02 - subjects allied to medicine > CAH02-02 - pharmacology, toxicology and pharmacy > CAH02-02-01 - pharmacology CAH02 - subjects allied to medicine > CAH02-05 - medical sciences > CAH02-05-03 - biomedical sciences (non-specific) |
||||||
| Divisions: | Faculty of Health, Education and Life Sciences > College of Life Sciences | ||||||
| Depositing User: | John Howl | ||||||
| Date Deposited: | 18 Sep 2024 11:37 | ||||||
| Last Modified: | 18 Sep 2024 11:37 | ||||||
| URI: | https://www.open-access.bcu.ac.uk/id/eprint/15843 |
Actions (login required)
 |
View Item |
Tools
Tools