title: Early growth response protein 1 upregulation and nuclear translocation by 2'-benzoyloxycinnamaldehyde induces prostate cancer cell death.
abstract: 2'-Benzoyloxycinnamaldehyde (BCA) induces apoptosis in human cancer cells through ROS generation. BCA upregulates proapoptotic genes such as activating transcription factor 3 (ATF3), NSAID-activated gene 1 protein (NAG-1), and growth arrest and DNA-damage-inducible protein alpha (GADD45A) in prostate cancer cells. These genes are known to be induced by transcription factor early growth response protein 1 (EGR1). BCA induces significant EGR1 upregulation, while EGR1 knockdown decreases the induction of these genes with concurrent alleviation of cell death by BCA. Antioxidant glutathione pretreatment with BCA removes EGR1 expression increase, suggesting that EGR1 upregulation is dependent on oxidative stress generated by BCA. In prostate cancer cells, EGR1 localizes in the cytoplasm; however, BCA remarkably upregulates EGR1 nuclear translocalization, suggesting its possible effect as a transcriptional activator. BCA induces transient upregulation of importin-7 (IPO7) which is critical for EGR1 nuclear translocation, and IPO7 knockdown led to a significant decrease in chemosensitivity to BCA. Taken together, our findings suggest that BCA induces prostate cancer cell death via EGR1 upregulation and nuclear translocalization, followed by activation of proapoptotic target genes.
authors.affiliation: Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kang
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Ock
authors.forename: Heon-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.forename: Su-Hyung
authors.initials: SH
authors.lastname: Hong
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005978:Glutathione / Q000494:pharmacology; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000097642:GADD45 Proteins
chemical_list: D000171:Acrolein; D051700:Activating Transcription Factor 3; D000970:Antineoplastic Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D001565:Benzoates; D018797:Cell Cycle Proteins; D051766:Early Growth Response Protein 1; D005978:Glutathione; D055436:Growth Differentiation Factor 15; D028884:Karyopherins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C484327:2'-benzoyloxycinnamaldehyde; C490449:ATF3 protein, human; C497325:EGR1 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C526140:GDF15 protein, human; C466996:IPO7 protein, human