title: Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells.
abstract: Daidzein, which belongs to the group of isoflavones from soybeans, has been extensively researched prostate, cervix, brain, breast, and colon cancer cell lines. However, daidzein has not been thoroughly investigated in human hepatic cancer cells; therefore, we investigated whether it inhibits hepatic cancer cell growth. Decreased cell proliferation was measured in daidzein-treated hepatic cancer cells (SK-HEP-1) upon real-time cell electronic sensing analysis however, it was not affected on normal human hepatocytes (Chang). Daidzein-induced apoptosis was demonstrated by comet and TUNEL assay. Moreover, we conducted two-dimensional electrophoresis to study the mechanism of daidzein-induced apoptosis in daidzein-treated SK-HEP-1 cells. Expression of peroxiredoxin-3 (Prdx-3), which modulates redox homeostasis of cells, was increased in protein analysis. Additionally, we measured the levels of reactive oxygen species and it was decreased in daidzein-treated SKHEP-1 cells. Daidzein-induced apoptosis in SK-HEP-1 cells was also associated with the up-regulation of Bak and down-regulation of Bcl-2 and Bcl-xL proteins. Moreover, daidzein treatment increased in the release of mitochondrial cytochrome c and activation of APAF-1, caspase 9 and caspase 3. Overall, these result indicate that daidzein is a potent inducer of apoptosis in hepatic cancer cells via mitochondrial pathway.
authors: Department of Biological Science, Gachon University, 534-2 Yeonsu-dong, Yeonsu-go, Incheon 406-799, Republic of Korea.
authors: Hyun Jin
authors: HJ
authors: Park
authors: Young Keul
authors: YK
authors: Jeon
authors: Dong Hun
authors: DH
authors: You
authors: Myeong Jin
authors: MJ
authors: Nam
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling; D007529:Isoflavones / Q000633:toxicity*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D061105:Peroxiredoxin III / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; C494772:BAK1 protein, human; D007529:Isoflavones; D017382:Reactive Oxygen Species; C090468:TP53BP2 protein, human; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C004742:daidzein; D045304:Cytochromes c; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Daidzein; Liver cancer; Proxiredoxin 3