Arsenic oxide (As2O3) has recently been reported to induce remission in a high percentage of patients with
acute promyelocytic leukemia (APL). The aim of this study was to investigate the effects of
As2O3 at therapeutic concentrations on cell viability and apoptosis on leukemic cells from patients with non-M3
acute myelogenous leukemia (AML) and to study the resistance profile compared to conventional AML drugs. Cells from 20 patients were exposed to therapeutic concentrations of
As2O3 continuously for 96 h.
As2O3 reduced the viability in blast cells from all the 20 tested patients compared to unexposed controls (p-value: 0.02 at 0.05 microM; <0.005 at 1.0 microM and higher concentrations). An increase in the apoptotic rate was also seen after incubation with
As2O3. Parallel to the incubation with
arsenic the in vitro sensitivity to a number of chemotherapeutic agents commonly used in AML was studied. Correlation coefficients for the in vitro sensitivity were highly significant between the conventional AML drugs except for
Ara-C. For
As2O3, all the correlation coefficients were negative and ranged between -0.05 and -0.51. Furthermore, increased P-gp expression in a multidrug resistant HL-60 cell line did not decrease the sensitivity to
As2O3 as compared to the parental cell line. Neither did a P-gp-transfected variant of the K562 cell line show decreased sensitivity to
As2O3. We conclude that
As2O3 at therapeutic concentrations induces apoptosis and cytotoxic effects in blast cells from patients with non-M3 AML, and that
As2O3 differs from conventional AML drugs with respect to the mechanisms that confer resistance to the drugs.