Differentiation and apoptosis in human malignant melanoma G-361 cells induced by 2-aminophenoxazine-3-one.

Abstract

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.

• Authors: Shigetaka Shimizu, Mamoru Suzuki, Keisuke Miyazawa, Tomohisa Yokoyama, Kazuma Ohyashiki, Kaori Miyazaki, Akihisa Abe, Akio Tomoda
• Journal: Oncology reports (Oncol Rep) Vol. 14 Issue 1 Pg. 41-6 (Jul 2005) ISSN: 1021-335X [Print] Greece
• PMID: 15944765 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one
• 3-amino-1,4a-dihydro-4a,8-dimethyl-2H-phenoxazine-2-one
• Melanins
• Oxazines
• 3-aminophenoxazone

Topics

• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Melanins (metabolism)
• Melanoma (genetics, metabolism, pathology)
• Oxazines (pharmacology)