Shimizu Shigetaka, Suzuki Mamoru, Miyazawa Keisuke, Yokoyama Tomohisa, Ohyashiki Kazuma, Miyazaki Kaori, Abe Akihisa, Tomoda Akio
Department of Otorhinolaryngology, Tokyo Medical University, 5-7-1 Nishishinjuku, Tokyo 160-0023, Japan.
Oncol Rep. 2005 Jul;14(1):41-6.
Inhibitory effects of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1), 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-2) and 2-aminophenoxazine-3-one (Phx-3), which were produced by the reaction of o-aminophenol and its derivatives with bovine hemoglobin, on the proliferation of human malignant melanoma G-361 cells were studied under various conditions. Phx-1 and Phx-3 showed anti-proliferative effects on human malignant melanoma G-361 cells, however Phx-2 did not. Phx-3, which exerted the strongest anti-proliferative effects, inhibited the proliferation of human malignant melanoma G-361 cells during 24 h incubation at concentrations of >or=10 microM. Apoptosis and G1 arrest in the cells, which were detected by DNA laddering on electrophoresis and flow cytometry, respectively, were observed when the melanoma G-361 cells were treated with Phx-3 at 37 degrees C for 24 h. Concomitantly, the increased melanin formation in G-361 cells was indicated by biochemical and morphological detection of melanin within 24 h exposure to Phx-3. The present results suggest that Phx-3 exclusively demonstrates anti-tumor activity against human malignant melanoma G-361 cells by inducing cell cycle accumulation at G1, differentiation and apoptosis.
邻氨基酚及其衍生物与牛血红蛋白反应生成的2-氨基-4,4α-二氢-4α,7-二甲基-3H-吩恶嗪-3-酮（Phx-1）、2-氨基-4,4α-二氢-4α,7-二甲基-3H-吩恶嗪-3-酮（Phx-2）和2-氨基吩恶嗪-3-酮（Phx-3）在不同条件下对人恶性黑色素瘤G-361细胞增殖的抑制作用进行了研究。Phx-1和Phx-3对人恶性黑色素瘤G-361细胞具有抗增殖作用，而Phx-2则没有。Phx-3具有最强的抗增殖作用，在浓度≥10μM时，在24小时孵育期间抑制人恶性黑色素瘤G-361细胞的增殖。当黑色素瘤G-361细胞在37℃用Phx-3处理24小时时，分别通过电泳DNA梯状条带和流式细胞术检测到细胞凋亡和G1期阻滞。同时，在暴露于Phx-3的24小时内，通过黑色素的生化和形态学检测表明G-361细胞中黑色素形成增加。目前的结果表明，Phx-3通过诱导细胞周期在G1期积累、分化和凋亡，专门显示出对人恶性黑色素瘤G-361细胞的抗肿瘤活性。
