Pregled bibliografske jedinice broj: 177538
Mechanism of action of ZIO-101 (S-dimethylarsino-glutathione), an organic arsenic derivative that is equally effective and less toxic than arsenic trioxide
Mechanism of action of ZIO-101 (S-dimethylarsino-glutathione), an organic arsenic derivative that is equally effective and less toxic than arsenic trioxide // Abstract Book
Zagreb, 2004. (poster, domaća recenzija, sažetak, znanstveni)
CROSBI ID: 177538 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Mechanism of action of ZIO-101 (S-dimethylarsino-glutathione), an organic arsenic derivative that is equally effective and less toxic than arsenic trioxide
Autori
Golemović, Mirna ; Kantarjian, H ; Oršolić, Nada ; Cheng, X ; Manshouri, T ; Zingaro, R ; Batinić, Drago ; Cortes, J ; Freireich, EJ ; Verstovšek, Srđan
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
Abstract Book
/ - Zagreb, 2004
Skup
7th seminar New trends in the treatment of acute leukemia
Mjesto i datum
Dubrovnik, Hrvatska, 11.09.2004. - 14.09.2004
Vrsta sudjelovanja
Poster
Vrsta recenzije
Domaća recenzija
Ključne riječi
arsenic trioxide; ZIO-101; apoptosis; PML/RARa; ROS; glutathione
Sažetak
Newly synthesized organic arsenic derivative ZIO-101 (S-dimethylarsino-glutathione) has comparable in vitro antileukemic activity to arsenic trioxide (ATO). However, ZIO-101 is significantly less toxic than ATO in in vitro and in vivo testing. We have evaluated the activity of ZIO-101 on several cellular compartments, reported as targets of ATO. ZIO-101 induced degradation of PML/RARa protein but treatment with ZIO-101 affected equally U937/PR9 cells that expressed PML/RARa in Zn2+ inducible manner regardless whether PML/RARa expression was induced or not ; ATO killed only cells with expressed protein. ZIO-101 induced G2/M arrest and apoptosis in NB4 and HL60 leukemic cells in time- and dose-dependent manner ; this activity was more abundant than in the case of ATO. All apoptotic events in HL60 cells were followed by PARP, caspase-9 and slight caspase-8 cleavage. We did not observe changes in protein levels of bcl-2, bcl-xl and bax. ZIO-101 induced significantly stronger H2O2 production in leukemic cells than ATO ; response to ZIO-101 was dependent on cells’ glutathione level. In conclusion, ZIO-101 primarily kills leukemic cells via induction of reactive oxygen species with subsequent apoptosis and cell cycle disturbance ; its activity does not depend on the presence of PML/RARa protein. Therefore, ZIO-101 should be evaluated against a broad spectrum of malignancies.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti
POVEZANOST RADA
