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Antitumor Effects of a Novel Phenoxazine Derivative on Human Leukemia Cell Lines in Vitro and in Vivo

First Department of Internal Medicine [T. S., K. O.] and Department of Biochemistry [A. T.], Tokyo Medical University, Tokyo 160-0023, Japan, and Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya 464, Japan [R. I.]

2-Amino-4,4-dihydro-4,7-dimethyl-3H-phenoxazine- 3-one (Phx) was synthesized by reacting 2-amino-5-methyl-phenol 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 the leukemia cell lines we tested, in a dose-dependent manner. We further investigated the antitumor effect of this compound on HAL-01-bearing nude mice. Treatment with Phx markedly reduced the tumor growth rate in the experimental 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 examined the effects of Phx on human normal hematopoietic progenitor cells by a clonogenic assay, and we observed less suppression of normal progenitor cells than of leukemic progenitors. These results suggest that Phx may be used to treat patients affected by different types of leukemia.

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