2-Aminophenoxazine-3-one Prevents Pulmonary Metastasis of Mouse B16 Melanoma Cells in Mice

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  • Hongo Takayuki
    Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, Japan
  • Miyano-Kurosaki Naoko
    Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, Japan
  • Kurosaki Kunihiko
    Department of Legal Medicine, School of Medicine, Toho University, Japan
  • Hata Akihiro
    Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, Japan
  • Harigae Satoko
    Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, Japan
  • Tomoda Akio
    Department of Biochemistry, Tokyo Medical University, Japan

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Abstract

2-Aminophenoxazine-3-one (Phx-3) induced cellular apoptosis in mouse melanoma B16 cells as detected by DNA laddering and upregulated Fas expression in the cells in vitro. Next, the anti-metastatic effects of Phx-3 were investigated in C56BL/6 mice. When B16 melanoma cells were injected into the tail veins of mice, significant metastasis of the cells was indicated in the lungs, 14 days after treatment. In contrast, when 0.5 mg/kg Phx-3 was administered to mice through the tail veins, once simultaneously with or every three days after the administration of B16 melanoma cells, the number of metastasized pulmonary cells was extremely reduced. Moderate reduction of the number of metastasized pulmonary cells was indicated in the mice with a single dose of Phx-3 on day 3 after injection of the cells. However, when Phx-3 was administered in a single dose, 6 or 9 days after the injection of the cells, the number of metastasized pulmonary cells remained the same. The present results indicate that the metastasis of mouse B16 melanoma cells to the lung was significantly inhibited in mice administered Phx-3, which activated the intrinsic and extrinsic apoptotic pathways. The present study suggests that Phx-3 might be a potential anti-metastatic agent as well as an anticancer agent.

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