title: Genistein induces apoptotic cell death associated with inhibition of the NF-κB pathway in adult T-cell leukemia cells.
abstract: We have shown that genistein inhibits the growth of adult T-cell leukemia (ATL) cells in vitro and in vivo, and this leads to pronounced G2/M arrest. This report shows that genistein induces apoptotic death in ATL cells. Although the pan-caspase inhibitor, Z-VAD-fmk, did not inhibit genistein-induced apoptosis, release of apoptosis-inducing factor (AIF) into the cytosol occurred. Poly-ADP ribose polymerase inhibition also abrogated genistein-induced apoptosis. Genistein decreased nuclear p65 translocation and IκBα phosphorylation, and downregulated the anti-apoptotic proteins, XIAP, cIAP and survivin, NF-κB-responsive gene products. Thus, genistein is a promising agent for ATL that induces caspase-independent apoptosis through inhibition of the NF-κB pathway.
authors.affiliation: Faculty of Agriculture, Department of Biochemistry and Applied Biosciences, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki 889-2192, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mine
authors.forename: Misato
authors.initials: M
authors.lastname: Nishimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morishita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishiyama
mesh_terms: D000328:Adult; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D019833:Genistein / Q000633:toxicity*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D051996:Transcription Factor RelA / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D016588:Anticarcinogenic Agents; D051033:Apoptosis Inducing Factor; C107489:BIRC5 protein, human; D061945:Caspase Inhibitors; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000077022:Survivin; D051996:Transcription Factor RelA; D051636:X-Linked Inhibitor of Apoptosis Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000072000:NF-KappaB Inhibitor alpha; D019833:Genistein; D011065:Poly(ADP-ribose) Polymerases