title: A short peptide derived from the gN helix domain of FGF8b suppresses the growth of human prostate cancer cells.
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.
authors.affiliation: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Wu
authors.initials: W
authors.lastname: Luo
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Ruixue
authors.initials: R
authors.lastname: Wang
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Zeng
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.forename: Xilei
authors.initials: X
authors.lastname: Chen
authors.forename: Susu
authors.initials: S
authors.lastname: Gao
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D043182:Carboxylesterase / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C496456:FGF8 protein, human; D008869:Microtubule-Associated Proteins; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D019938:Cyclin D1; D051524:Fibroblast Growth Factor 8; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D043182:Carboxylesterase; C020118:ESD protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C523923:PAFAH1B2 protein, human
keywords: FGF8b; Proliferation; Prostate cancer; gN helix