title: The induction of activating transcription factor 3 (ATF3) contributes to anti-cancer activity of Abeliophyllum distichum Nakai in human colorectal cancer cells.
abstract: BACKGROUND
  Recently, Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme. However, no specific pharmacological effects from A. distichum have been described. We performed in vitro study to evaluate anti-cancer properties of A. distichum and then elucidate the potential mechanisms.
  
  
  METHODS
  Cell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA.
  
  
  RESULTS
  Exposure of ethyl acetate fraction from the parts of A. distichum including flower, leaf and branch to human colorectal cancer cells, breast cancer cells and hepatocellular carcinoma reduced the cell viability. The branch extracts from A. distichum (EAFAD-B) increased the expression of activating transcription factor 3 (ATF3) and promoter activity, indicating transcriptional activation of ATF3 gene by EAFAD-B. In addition, our data showed that EAFAD-B-responsible sites might be between -147 and -85 region of the ATF3 promoter. EAFAD-B-induced ATF3 promoter activity was significantly decreased when the CREB site was deleted. However, the deletion of Ftz sites did not affect ATF3 promoter activity by EAFAD-B. We also observed that inhibition of p38MAPK and GSK3β attenuated EAFAD-B-mediated ATF3 promoter activation. Also, EAFAD-B contributes at least in part to increase of ATF3 accumulation.
  
  
  CONCLUSIONS
  These findings suggest that the anti-cancer activity of EAFAD-B may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression.
authors.forename: Gwang Hun
authors.initials: GH
authors.lastname: Park
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Eo
authors.forename: Hun Min
authors.initials: HM
authors.lastname: Song
authors.forename: So Hee
authors.initials: SH
authors.lastname: Woo
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Lee
authors.forename: Man Hyo
authors.initials: MH
authors.lastname: Lee
authors.forename: Jeong Rak
authors.initials: JR
authors.lastname: Lee
authors.forename: Jin Suk
authors.initials: JS
authors.lastname: Koo
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Korea. jjb0403@anu.ac.kr.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
mesh_terms: D051700:Activating Transcription Factor 3 / Q000096:biosynthesis*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D029592:Oleaceae; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3