Anti-Leukemic Effect of Tetra-Arsenic Oxide in Acute Promyelocytic Leukemia Cells in Vitro and In Vivo

Abstract 4306

Arsenic trioxide (As₂O₃; ATO) has been established to be an effective agent for treating acute promyelocytic leukemia (APL). Tetra-arsenic oxide (As₄O₆; TAO) is a new arsenic compound which has shown anti-proliferative and apoptosis-inducing effects against human leukemic and solid tumor cells, but TAO has never been studied in APL so far. We investigated the effect of TAO in APL cell lines (NB-4), and evaluated their anti-leukemic effect in murine xenograft model. In both the XTT assay and in FACS analysis, TAO inhibited cell proliferation and induced apoptosis in NB4 cell lines as effective as ATO in dose dependent manner. In FACS analysis, TAO induced apoptosis in NB4 cell lines as effective as ATO in a dose dependent manner. However, expression of differentiation (CD11b) was unchanged. For in vivo study, we established a xenograft model in nude mice (BALB/cBy J-nu) using the NB4 cell line. 1 × 10⁷ NB4 cells were inoculated into the flank subcutaneously. When the tumor size reached 1.0 cm³, intra-peritoneal ATO or TAO treatment (5mg/kg or 10mg/kg) was initiated and administration was performed daily. We found that TAO (10mg/kg) significantly inhibited tumor growth of the inoculated NB4 cell as effective as ATO (10mg/kg). These results suggest that TAO may have a potential for the treatment of APL.