title: The milk-derived fusion peptide, ACFP, suppresses the growth of primary human ovarian cancer cells by regulating apoptotic gene expression and signaling pathways.
abstract: BACKGROUND
  ACFP is an anti-cancer fusion peptide derived from bovine milk protein. This study was to investigate the anti-cancer function and underlying mechanisms of ACFP in ovarian cancer.
  
  
  METHODS
  Fresh ovarian tumor tissues were collected from 53 patients who underwent initial debulking surgery, and primary cancer cells were cultured. Normal ovarian surface epithelium cells (NOSECs), isolated from 7 patients who underwent surgery for uterine fibromas, were used as normal control tissue. Anti-viabilities of ACFP were assessed by WST-1 (water-soluble tetrazolium 1), and apoptosis was measured using a flow cytometry-based assay. Gene expression profiles of ovarian cancer cells treated with ACFP were generated by cDNA microarray, and the expression of apoptotic-specific genes, such as bcl-xl, bax, akt, caspase-3, CDC25C and cyclinB1, was assessed by real time PCR and western blot analysis.
  
  
  RESULTS
  Treatment with ACFP inhibited the viability and promoted apoptosis of primary ovarian cancer cells but exhibited little or no cytotoxicity toward normal primary ovarian cells. Mechanistically, the anti-cancer effects of ACFP in ovarian cells were shown to occur partially via changes in gene expression and related signal pathways. Gene expression profiling highlighted that ACFP treatment in ovarian cancer cells repressed the expression of bcl-xl, akt, CDC25C and cyclinB1 and promoted the expression of bax and caspase-3 in a time- and dose-dependent manner.
  
  
  CONCLUSIONS
  Our results suggest that ACFP may represent a potential therapeutic agent for ovarian cancer that functions by altering the expression and signaling of cancer-related pathways in ovarian cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Mengjing
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Yigui
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gu
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, 230032, China. yideqin@ahmu.edu.cn.
authors.forename: Yide
authors.initials: Y
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008894:Milk Proteins / Q000008:administration & dosage*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010455:Peptides / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D020687:cdc25 Phosphatases / Q000096:biosynthesis
chemical_list: D056744:Cyclin B1; D008894:Milk Proteins; D010455:Peptides; D051028:bcl-2-Associated X Protein; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D053148:Caspase 3
keywords: Anti-ovarian cancer; Apoptosis; Cell viability; Fusion peptide; cDNA microarray