title: (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-κB/STAT3 pathway.
abstract: Ovarian cancer is a cancerous growth arising from the ovary and with poor prognosis that usually have resistant to all currently available treatments. Whether (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (butenal) synthesized by Maillard reaction from fructose-tyrosine, has potential therapeutic activity against human ovarian cancer was investigated using two ovarian cancer cell lines (PA-1, SK-OV-3). We found that butenal could inhibit NF-κB/STAT3 activity, thereby inducing apoptotic cell death of ovarian cancer cells. We treated with several concentration of butenal each cell line differently (PA-1; 5, 10 and 15 μg/ml, SK-OV-3; 10, 20 and 30 μg/ml). First, ovarian cancer cell lines exhibited constitutively active NF-κB, and treatment with butenal abolished this activation as indicated by DNA binding activity. Second, butenal suppressed activation of signal transducer and activator of transcription-3 as indicated by decreased phosphorylation and inhibition of Janus kinase-2 phosphorylation. Third, butenal induced expression of pro-apoptotic proteins such as proteolytic cleavage of PARP, Bax and activation of caspase-3, -8 and -9. Lastly, combination of butenal and TRAIL causes enhanced induction of apoptosis. Overall, our results indicate that butenal mediates its anti-proliferative and apoptotic effects through activation of multiple cell signaling pathways and enhances the TRAIL-induced apoptosis. These data suggested that butenal may be a potential anti-cancer agent in ovarian cancer.
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Ch'ongju, 361-763, Chungbuk, Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Cho
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Hee Peom
authors.initials: HP
authors.lastname: Lee
authors.forename: Myong Ki
authors.initials: MK
authors.lastname: Back
authors.forename: Ha Chang
authors.initials: HC
authors.lastname: Sung
authors.forename: Hee Won
authors.initials: HW
authors.lastname: Chang
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Heon-Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: C580808:2,4-bis(p-hydroxyphenyl)-2-butenal; D000447:Aldehydes; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D010636:Phenols; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt