title: 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242) induces apoptosis via modulating E7 expression and inhibition of PI3K/Akt pathway in SiHa human cervical cancer cells.
abstract: The Maillard reaction is a chemical reaction occurring between an amino acid and a reducing sugar, usually requiring thermal processing. Maillard reaction products (MRPs) have antioxidant, antimutagenic, and antibacterial effects, and although 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242), a fructose-tyrosine MRP, appears to inhibit proliferation of cancer cells, its mechanism of action has not been studied in detail. We found that HPB242 treatment modulated expression of cyclins and tumor suppressor genes in SiHa human cervical cancer cell lines: cyclins and phospho-pRB were downregulated, whereas the expression of CDK inhibitors and p53 was enhanced. HPB242 induced apoptosis dose-dependently by suppressing E7 expression and leading to sub-G1 cell-cycle arrest in SiHa cell lines; treatment also led to the proteolytic cleavage of caspase-3, -9, and poly (ADP-ribose) polymerase. Moreover, HPB242 upregulated Fas expression, altered expressions of pro- and antiapoptotic factors, and also inhibited nuclear translocation of nuclear factor κB and phosphorylation of IκB. HPB242 treatment decreased phosphatidyl inositol-3 kinase and p-Akt expression levels, demonstrating that this survival pathway may also be inhibited by HPB242. Cumulatively, HPB242 promotes apoptosis by influencing E7 expression, inducing cell-cycle arrest at sub-G1 phase, and promoting both intrinsic (mitochondrial) and extrinsic (Fas-dependent) apoptosis in SiHa human cervical cancer cells.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea.
authors.forename: Man Sub
authors.initials: MS
authors.lastname: Kim
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Yesol
authors.initials: Y
authors.lastname: Bak
authors.forename: Yun Sun
authors.initials: YS
authors.lastname: Park
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Kang
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Heon Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015416:Maillard Reaction; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D010636:Phenols / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C580808:2,4-bis(p-hydroxyphenyl)-2-butenal; D000447:Aldehydes; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D050725:Papillomavirus E7 Proteins; D010636:Phenols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000072000:NF-KappaB Inhibitor alpha; D051057:Proto-Oncogene Proteins c-akt