The contribution of activating transcription factor 3 to apoptosis of human colorectal cancer cells by protocatechualdehyde, a naturally occurring phenolic compound.

Abstract

Protocatechualdehyde (PCA) is one of the important compounds found in barley, green cavendish bananas and grapevine leaves. PCA shows anti-cancer activities in breast, leukemia and colorectal cancer cells. Previous study reported that PCA exerts anti-cancer activity through down-regulating cyclin D1 and HDAC2 in human colorectal cancer cells. However, the underlying mechanisms for the expression of activating transcription factor 3 (ATF3) by PCA has not been studied. Thus, we performed in vitro study to investigate if treatment of PCA affects ATF3 expression and ATF3-mediated apoptosis in human colorectal cancer cells. PCA decreased cell viability in a dose-dependent manner in HCT116 and SW480 cells. In addition, PCA reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. Exposure of PCA activated the levels of ATF3 protein and mRNA in HCT116 and SW480 cells. Inhibition of ERK1/2/ by PD98059 and p38 by SB203580 inhibited PCA-induced ATF3 expression and transcriptional activation. ATF3-knockdown inhibited PCA-induced apoptosis and cell viability. In addition, ATF3 overexpression enhanced PCA-mediated cleavage of PARP. These findings suggest that inhibition of cell viability and apoptosis by PCA may be result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.

• Authors: Jeong Rak Lee, Man Hyo Lee, Hyun Ji Eo, Gwang Hun Park, Hun Min Song, Mi Kyoung Kim, Jin Wook Lee, Jin Boo Jeong
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 564 Pg. 203-10 (Dec 15 2014) ISSN: 1096-0384 [Electronic] United States
• PMID: 25447816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• ATF3 protein, human
• Activating Transcription Factor 3
• Anticoagulants
• Benzaldehydes
• Catechols
• Neoplasm Proteins
• protocatechualdehyde
• Poly(ADP-ribose) Polymerases
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases

Topics

• Activating Transcription Factor 3 (biosynthesis, genetics)
• Anticoagulants (pharmacology)
• Apoptosis (drug effects, genetics)
• Benzaldehydes (pharmacology)
• Catechols (pharmacology)
• Colorectal Neoplasms (drug therapy, genetics, metabolism)
• Down-Regulation (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Hep G2 Cells
• Humans
• MAP Kinase Signaling System (drug effects, genetics)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)