This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hara, K. Articles by Kang, D. Search for Related Content PubMed PubMed Citation Articles by Hara, K. Articles by Kang, D.

¹ Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka; ² Center for Gene Research, Yamaguchi University, Yamaguchi; ³ Department of Immunology, Juntendo University School of Medicine; ⁴ Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo; and ⁵ Department of Biochemistry and Research Institute of Immunological Treatment, Tokyo Medical University, Tokyo, Japan

Requests for reprints: Dongchon Kang, Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi, Fukuoka 812-8582, Japan. Phone: 81-92-642-5749; Fax: 81-92-642-5772. E-mail: kang{at}mailserver.med.kyushu-u.ac.jp

2-Amino-4,4-dihydro-4,7-dimethyl-3H-phenoxazine-3-one (Phx-1) has been developed as a novel phenoxazine derivative having an anticancer activity on a variety of cancer cell lines as well as transplanted tumors in mice with minimal toxicity to normal cells. We examined the effects of Phx-1 on Jurkat cells, a human T cell line. Phx-1 inhibited proliferation of the cells in a dose-dependent manner but hardly induced cell death, suggesting that Phx-1 acts primarily as an antiproliferative reagent but not as a cytocidal drug. Phx-1 enhanced tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)-induced apoptotic cell death about 100-fold. Tumor necrosis factor , which alone does not induce cell death of Jurkat cells, caused apoptosis in combination with Phx-1. These enhancements of cell death were not due to up-regulation of the death receptors. Phx-1 decreased serum-induced phosphorylation of Akt, a kinase involved in cell proliferation and survival, and inhibited complex III of mitochondrial respiratory chain. Considering that both TRAIL and Phx-1 have only marginal cytotoxicity to most normal cells, Phx-1 may provide an ideal combination for cancer therapy with TRAIL.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 3/10/05; revised 4/13/05; accepted 4/29/05.