title: Se-Allylselenocysteine induces autophagy by modulating the AMPK/mTOR signaling pathway and epigenetic regulation of PCDH17 in human colorectal adenocarcinoma cells.
abstract: METHODS
  Selenium (Se)-conjugated compounds have been established as anti-carcinogenic compounds. The use of chemicals as cancer chemotherapeutic agents to induce programmed cell death (PCD) involves genetic and epigenetic modifications. In this study, we investigated the underlying molecular mechanisms of Se-allylselenocysteine (ASC)-induced PCD and protocadherin 17 (PCDH17) expression in HT-29 cells.
  
  
  RESULTS
  Cell viability analysis indicated that the ability of ASC to induce cancer cell death was greater than that of Se-methylselenocysteine in colorectal cancer cells. ASC also decreased global DNA methylation levels via downregulation of DNA methyltransferase 1 expression. The autophagic cell death is the cause in ASC-induced cytotoxicity that was inhibited by pretreatment with autophagy inhibitor. At the molecular level, ASC induced PCDH17 expression through decreased PCDH17 promoter hypermethylation. PCDH17 is also an important role in ASC-induced autophagy by HT-29 transfected with PCDH17 shRNA or expression plasmid. Our western blot analysis showed that ASC significantly induced autophagy via the AMPK/mTOR pathway that was also regulated PCDH17 expression. Additionally, we used the HT-29 tumor xenograft models to confirm the ability of ASC inhibited tumor growth.
  
  
  CONCLUSIONS
  These results reveal that ASC is an effective inducer of autophagy through regulating the AMPK/mTOR and PCDH17 expression via epigenetic modification.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan.
authors.forename: Fang-Zong
authors.initials: FZ
authors.lastname: Wang
authors.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Tsai
authors.affiliation: Department of Food Science, National Chiayi University, Chiayi, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Lo
authors.affiliation: American Medical Holdings Inc, New York, NY, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.|Department of Biomedical Informatics, Asia University, Taichung, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.|Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; C529349:PCDH17 protein, human; C415427:Se-allylselenocysteine; D017279:Selenocysteine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C002979:selenomethylselenocysteine
keywords: Autophagy; DNA methylation; Epigenetic; PCDH17; Se-allylselenocysteine