Antitumor effects of a novel phenoxazine derivative on human leukemia celllines in vitro and in vivo

2-Amino-4,4 alpha -dihydro-4 alpha ,7-dimethyl-3H-phenoxazine-3-one (Phx) w as synthesized by reacting 2-amino-5-methylphenol with bovine hemolysates. Because Phx is a phenoxazine derivative like actinomycin D, we examined its effects on the proliferation of the human leukemia cell lines K562, HL-60, and HAL-01. Phx inhibited proliferation and induced apoptosis in all of th e leukemia cell lines we tested, in a dose-dependent manner. We further inv estigated the antitumor effect of this compound on BAL-Ol-bearing nude mice . Treatment with Phx markedly reduced the tumor growth rate in the experime ntal group, as compared with the control group. Moreover, Phx was found to have few adverse effects on weight loss and WBC count. In addition, we exam ined the effects of Phx on human normal hematopoietic progenitor cells by a clonogenic assay, and we observed less suppression of normal progenitor ce lls than of leukemic progenitors, These results suggest that Phx may be use d to treat patients affected by different types of leukemia.