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: Hye-Sook Kang, Jiyeon Ock, Heon-Jin Lee, Yu-Jin Lee, Byoung-Mog Kwon, Su-Hyung Hong
• Journal: Cancer letters (Cancer Lett) Vol. 329 Issue 2 Pg. 217-27 (Feb 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23178451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 2'-benzoyloxycinnamaldehyde
• ATF3 protein, human
• Activating Transcription Factor 3
• Antineoplastic Agents
• Antioxidants
• Apoptosis Regulatory Proteins
• Benzoates
• Cell Cycle Proteins
• EGR1 protein, human
• Early Growth Response Protein 1
• GADD45A protein, human
• GDF15 protein, human
• Growth Differentiation Factor 15
• IPO7 protein, human
• Karyopherins
• Nuclear Proteins
• RNA, Small Interfering
• Receptors, Cytoplasmic and Nuclear
• Acrolein
• Glutathione

Topics

• Acrolein (analogs & derivatives, pharmacology)
• Activating Transcription Factor 3 (genetics, metabolism)
• Active Transport, Cell Nucleus
• Antineoplastic Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Benzoates (pharmacology)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Nucleus (drug effects, metabolism)
• Cell Survival (drug effects)
• Early Growth Response Protein 1 (genetics, metabolism)
• Gene Expression (drug effects)
• Gene Knockdown Techniques
• Glutathione (pharmacology)
• Growth Differentiation Factor 15 (genetics, metabolism)
• Humans
• Karyopherins (genetics, metabolism)
• Male
• Nuclear Proteins (genetics, metabolism)
• Prostatic Neoplasms
• RNA, Small Interfering (genetics)
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Up-Regulation (drug effects)