title: Induction of G2/M phase arrest and apoptosis by a novel enediyne derivative, THDB, in chronic myeloid leukemia (HL-60) cells.
abstract: (Z)-2-(6-(Thieanisyl-2-yl)hexa-3-en-1,5-diynyl)benzenamine (THDB), an enediyne compound, was identified in our laboratory as a novel antineoplastic agent with broad spectrum of antitumor activities against many human cancer cells. THDB was found to inhibit the growth of HL-60 cells in a time-and dose-dependent manner. Cell cycle analysis showed G2/M phase arrest in HL-60 cells following 48 h exposure to THDB. Analysis of the cell cycle regulatory proteins demonstrated that THDB did not change the steady-state levels of cyclin B1, cyclin E, Cdk1 and Cdc25C, but decreased the protein levels of Cdk2 and cyclin A. THDB also caused a marked increase in apoptosis, as characterized by DNA fragmentation (DNA ladder and sub G1 formation), and poly (ADP-ribose) polymerase (PARP) cleavage, which was associated with activation of caspase-3, caspase-8 and caspase-9. Moreover, the THDB-induced apoptosis was significantly attenuated in the presence of specific inhibitors of caspase-3, -8 and -9. These molecular alterations provide an insight into THDB-caused growth inhibition, G2/M arrest and apoptotic death of HL-60 cells.
authors.affiliation: Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, 100 Shi-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC.
authors.forename: Yu-Jhang
authors.initials: YJ
authors.lastname: Lu
authors.forename: Sheng-Huei
authors.initials: SH
authors.lastname: Yang
authors.forename: Ching-Ming
authors.initials: CM
authors.lastname: Chien
authors.forename: Yi-Hsiung
authors.initials: YH
authors.lastname: Lin
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Hu
authors.forename: Zchong-Zcho
authors.initials: ZZ
authors.lastname: Wu
authors.forename: Ming-Jung
authors.initials: MJ
authors.lastname: Wu
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053281:Enediynes / Q000138:chemical synthesis / Q000633:toxicity*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C518618:(Z)-2-(6-(thieanisyl-2-yl)hexa-3-en-1,5-diynyl)benzenamine; D000199:Actins; D000970:Antineoplastic Agents; D053281:Enediynes; D013778:Tetrazolium Salts; D013844:Thiazoles; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; C022616:thiazolyl blue