title: Anti-cancer activity of Ginger (Zingiber officinale) leaf through the expression of activating transcription factor 3 in human colorectal cancer cells.
abstract: BACKGROUND
  Ginger leaf (GL) has long been used as a vegetable, tea and herbal medicine. However, its pharmacological properties are still poorly understood. Thus, we performed in vitro studies to evaluate anti-cancer properties of ginger leaf and then elucidate the potential mechanisms involved.
  
  
  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 GL to human colorectal cancer cells (HCT116, SW480 and LoVo cells) reduced the cell viability and induced apoptosis in a dose-dependent manner. In addition, GL reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. ATF3 knockdown attenuated GL-mediated apoptosis. GL increased activating transcription factor 3 (ATF3) expressions in both protein and mRNA level and activated ATF3 promoter activity, indicating transcriptional activation of ATF3 gene by GL. In addition, our data showed that GL-responsible sites might be between -318 and -85 region of the ATF3 promoter. We also observed that ERK1/2 inhibition by PD98059 attenuated GL-mediated ATF3 expression but not p38 inhibition by SB203580, indicating ERK1/2 pathway implicated in GL-induced ATF3 activation.
  
  
  CONCLUSIONS
  These findings suggest that the reduction of cell viability and apoptosis by GL may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression through ERK1/2 activation in human colorectal cancer cells.
authors.forename: Gwang Hun
authors.initials: GH
authors.lastname: Park
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Hun Min
authors.initials: HM
authors.lastname: Song
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Eo
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: Kiu-Hyung
authors.initials: KH
authors.lastname: Cho
authors.forename: Jeong Rak
authors.initials: JR
authors.lastname: Lee
authors.forename: Hyeon Je
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, South Korea. jjb0403@anu.ac.kr.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D051700:Activating Transcription Factor 3; D000970:Antineoplastic Agents; D010936:Plant Extracts