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A short peptide derived from the gN helix domain of FGF8b suppresses the growth of human prostate cancer cells.
- Source :
-
Cancer letters [Cancer Lett] 2013 Oct 10; Vol. 339 (2), pp. 226-36. Date of Electronic Publication: 2013 Jun 14. - Publication Year :
- 2013
-
Abstract
- Previous studies have demonstrated that fibroblast growth factor 8b (FGF8b) is up-regulated in a large proportion of prostate cancer patients and that it plays a key role in prostate carcinogenesis. In this study, we designed and synthesized a gN helix domain derived short peptide (termed 8b-13) based on the analysis of the FGF8b-FGFR structure. The synthetic peptides inhibited the proliferation of prostate cancer cell lines, including PC-3 and DU-145 cells. Further investigations indicated that 8b-13 arrested the cell cycle at the G0/G1 phase, reduced the activation of the Erk1/2, P38, and Akt cascades, and down-regulated the expression of G1/S-specific cyclinD1. The suppression of DNA synthesis and the G1 to S phase transition due to the expression of proteins related to proliferation and cell cycle progression may contribute to the inhibitory effect of 8b-13 peptides on cellular proliferation. Our results not only suggest that 8b-13 exerts an antitumor effect in prostate cancer but also confirm the essential role of the gN helix domain in mediating the activity of FGF8b.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- 1-Alkyl-2-acetylglycerophosphocholine Esterase genetics
1-Alkyl-2-acetylglycerophosphocholine Esterase metabolism
Amino Acid Sequence
Carboxylesterase genetics
Carboxylesterase metabolism
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Cyclin D1 genetics
Cyclin D1 metabolism
Fibroblast Growth Factor 8 chemistry
Fibroblast Growth Factor 8 pharmacology
Gene Expression
Gene Expression Regulation, Neoplastic drug effects
Humans
Male
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Mitogen-Activated Protein Kinases metabolism
Peptides chemistry
Proliferating Cell Nuclear Antigen genetics
Proliferating Cell Nuclear Antigen metabolism
Prostatic Neoplasms genetics
Proteomics methods
Proto-Oncogene Proteins c-akt metabolism
Receptors, Retinoic Acid genetics
Receptors, Retinoic Acid metabolism
Reproducibility of Results
Signal Transduction drug effects
Fibroblast Growth Factor 8 metabolism
Peptides pharmacology
Prostatic Neoplasms metabolism
Protein Interaction Domains and Motifs
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 339
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 23774400
- Full Text :
- https://doi.org/10.1016/j.canlet.2013.06.001