title: In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells.
abstract: Phlorofucofuroeckol A (PFF-A), one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB), located between positions -147 and -85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK), glycogen synthase kinase (GSK) 3β, and IκB kinase (IKK)-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose) polymerase (PARP) by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 36729, Korea. ehj56@naver.com.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Eo
authors.affiliation: Chuncheon Bioindustry Foundation, Chuncheon 24234, Korea. taehyung0218@naver.com.
authors.forename: Tae-Hyung
authors.initials: TH
authors.lastname: Kwon
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 36729, Korea. enter0230@hanmail.net.
authors.forename: Gwang Hun
authors.initials: GH
authors.lastname: Park
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 36729, Korea. ou1@dreamwiz.com.
authors.forename: Hun Min
authors.initials: HM
authors.lastname: Song
authors.affiliation: Department of Herbal Medicine Resource, Kangwon National University, Dogye 25949, Korea. withsj0830@naver.com.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Gyeongbuk Institute for Marine Bioindustry, Uljin 36315, Korea. pnh863660@gimb.or.kr.
authors.forename: Nyun-Ho
authors.initials: NH
authors.lastname: Park
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 36729, Korea. jjb0403@anu.ac.kr.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004147:Dioxins / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D000970:Antineoplastic Agents; D001572:Benzofurans; D004147:Dioxins; C064093:phlorofucofuroeckol A; D050882:CREB-Binding Protein; D000071679:Glycogen Synthase Kinase 3 beta; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Eisenia bicyclis; activating transcription factor 3; apoptosis; human colorectal cancer; phlorofucofuroeckol A