title: 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.affiliation: Gyeongbuk Institute for Bio-industry, Andong 760380, Republic of Korea.
authors.forename: Jeong Rak
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Gyeongbuk Institute for Bio-industry, Andong 760380, Republic of Korea.
authors.forename: Man Hyo
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Eo
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Gwang Hun
authors.initials: GH
authors.lastname: Park
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Hun Min
authors.initials: HM
authors.lastname: Song
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea; Institute of Agricultural Science and Technology, Andong National University, Andong 760749, Republic of Korea. Electronic address: jjb0403@anu.ac.kr.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
mesh_terms: D051700:Activating Transcription Factor 3 / Q000096:biosynthesis* / Q000235:genetics; D000925:Anticoagulants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001547:Benzaldehydes / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D000925:Anticoagulants; D001547:Benzaldehydes; D002396:Catechols; D009363:Neoplasm Proteins; C005581:protocatechualdehyde; D011065:Poly(ADP-ribose) Polymerases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Activating transcription factor 3; Apoptosis; Chemoprevention; Colorectal cancer; Protocatechualdehyde