Cargando…
Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway
We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S pha...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165336/ https://www.ncbi.nlm.nih.gov/pubmed/30208576 http://dx.doi.org/10.3390/md16090325 |
_version_ | 1783359812851990528 |
---|---|
author | Li, Xiaojuan Tang, Yunping Yu, Fangmiao Sun, Yu Huang, Fangfang Chen, Yan Yang, Zuisu Ding, Guofang |
author_facet | Li, Xiaojuan Tang, Yunping Yu, Fangmiao Sun, Yu Huang, Fangfang Chen, Yan Yang, Zuisu Ding, Guofang |
author_sort | Li, Xiaojuan |
collection | PubMed |
description | We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future. |
format | Online Article Text |
id | pubmed-6165336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61653362018-10-11 Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway Li, Xiaojuan Tang, Yunping Yu, Fangmiao Sun, Yu Huang, Fangfang Chen, Yan Yang, Zuisu Ding, Guofang Mar Drugs Article We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future. MDPI 2018-09-11 /pmc/articles/PMC6165336/ /pubmed/30208576 http://dx.doi.org/10.3390/md16090325 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Xiaojuan Tang, Yunping Yu, Fangmiao Sun, Yu Huang, Fangfang Chen, Yan Yang, Zuisu Ding, Guofang Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway |
title | Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway |
title_full | Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway |
title_fullStr | Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway |
title_full_unstemmed | Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway |
title_short | Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway |
title_sort | inhibition of prostate cancer du-145 cells proliferation by anthopleura anjunae oligopeptide (yvpgp) via pi3k/akt/mtor signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165336/ https://www.ncbi.nlm.nih.gov/pubmed/30208576 http://dx.doi.org/10.3390/md16090325 |
work_keys_str_mv | AT lixiaojuan inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT tangyunping inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT yufangmiao inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT sunyu inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT huangfangfang inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT chenyan inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT yangzuisu inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway AT dingguofang inhibitionofprostatecancerdu145cellsproliferationbyanthopleuraanjunaeoligopeptideyvpgpviapi3kaktmtorsignalingpathway |