title: CDA-II, a urinary preparation, induces growth arrest and apoptosis of human leukemia cells through inactivation of nuclear factor-kappaB in a caspase-dependent manner.
abstract: CDA-II (cell differentiation agent II) was a urinary preparation, isolated from healthy human urine. We determined the anticancer activity of CDA-II using human acute myeloid leukemia (AML) cell lines, K562, Kasumi-1 and KG-1. An in vitro cytotoxicity assay showed that CDA-II exhibited growth arrest in leukemic cells, while it did not induce cytotoxicity in normal peripheral blood mononuclear cells (PBMCs). In vivo studies using the Kasumi-1 xenografted SCID mouse model showed tumor inhibition rate were increased and the survival time were prolonged in a dose-dependent manner, without any significant toxicity on mice body. Depolarized mitochondrial membranes and the activation of caspase-3, 9 as well as PARP were found in leukemic cells treated with CDA-II for 6-24h. We further found NF-kappaB nuclear translocation were prevented by CDA-II treatment, which therefore inactivated NF-kappaB and down-regulated its target genes expression, including Bcl-2/Bax ratio, Mcl-1 and XIAP. The caspase-3 inhibitor Z-DEVD-FMK inhibited CDA-II-induced apoptosis and CDA-II combined with NF-kappaB inhibitor PDTC significantly increased the apoptotic rate of leukemic cells. We concluded that CDA-II potently induced caspase-dependent leukemia-specific apoptosis in leukemic cells mediated through inactivation of NF-kappaB, involving in Bcl-2 family and XIAP, which has no cytotoxicity on normal cells.
authors.affiliation: Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, #79 Qingchun Road, Hangzhou, Zhejiang 310003, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Jin