Differentiation and apoptosis in human malignant melanoma G-361 cells induced by 2-aminophenoxazine-3-one.
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.
Shimizu
Shigetaka
S
Department of Otorhinolaryngology, Tokyo Medical University, 5-7-1 Nishishinjuku, Tokyo 160-0023, Japan.
Suzuki
Mamoru
M
Miyazawa
Keisuke
K
Yokoyama
Tomohisa
T
Ohyashiki
Kazuma
K
Miyazaki
Kaori
K
Abe
Akihisa
A
Tomoda
Akio
A
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010078:Oxazines / Q000494:pharmacology*
C104202:2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one; C470370:3-amino-1,4a-dihydro-4a,8-dimethyl-2H-phenoxazine-2-one; D008543:Melanins; D010078:Oxazines; C005512:3-aminophenoxazone