title: Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan.
abstract: The putative functions of the cellular prion protein (PrP(c)) are believed to be associated with cell signaling, differentiation, survival, and cancer progression. With respect to cancer development and progression, elevations and mutations of PrP(c) expression have been shown to increase the risk for malignancy and metastasis in breast and colorectal cancer. Since both natural supplements and direct regulation of PrP(c) expression contribute to inhibition of cancer progression and growth, we hypothesized that knockdown of PrP(c) could lead to an enhanced synergic effect on the inhibition of cancer growth by fucoidan.
  
  
  
  PrP(c) expression was suppressed in HT29 human colon cancer cells by utilizing small-interfering RNA (si-PRNP), and cells were subsequently used to study the antiproliferative and anticancer effects of fucoidan treatment of HT29 human colon cancer cells.
  
  
  
  Fucoidan treatment significantly inhibited growth and reduced cyclin and cyclin-dependent kinase (CDK) expression in HT29 colon cancer cells. Furthermore, silencing PrP(c) expression with si-PRNP amplified the fucoidan-induced changes in cell proliferation, apoptosis, and migration. Intraperitoneal injection of si-PRNP with fucoidan reduced proliferation and tumor volume in Balb/c nude mice. This enhanced antitumor efficacy was associated with decreased angiogenesis.
  
  
  
  Combination of fucoidan with silencing of PrP(c) has a synergic effect on the inhibition of HT29 colon cancer cell growth. Furthermore, we provide evidence for the therapeutic application of PrP(c) silencing with other anticancer drugs for cancer.
authors.affiliation: Medical Science Research Institute, Soonchunhyang University, Seoul Hospital, Seoul, Republic of Korea Department of Medical Bioscience, Soonchunhyang University, Asan, Republic of Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Yun
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Seungpil
authors.initials: S
authors.lastname: Yun
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. jhlee0407@sch.ac.kr.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Medical Science Research Institute, Soonchunhyang University, Seoul Hospital, Seoul, Republic of Korea Department of Medical Bioscience, Soonchunhyang University, Asan, Republic of Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Han
authors.affiliation: Medical Science Research Institute, Soonchunhyang University, Seoul Hospital, Seoul, Republic of Korea Department of Medical Bioscience, Soonchunhyang University, Asan, Republic of Korea.
authors.forename: Yeo Min
authors.initials: YM
authors.lastname: Yoon
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Daniel
authors.initials: D
authors.lastname: An
authors.affiliation: Medical Science Research Institute, Soonchunhyang University, Seoul Hospital, Seoul, Republic of Korea Department of Medical Bioscience, Soonchunhyang University, Asan, Republic of Korea jhlee0407@sch.ac.kr.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy; D020868:Gene Silencing; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D000072002:Prion Proteins / Q000235:genetics* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011134:Polysaccharides; D000072002:Prion Proteins; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C007789:fucoidan; D053148:Caspase 3
keywords: Fucoidan; cellular prion protein; migration; proliferation