Prevention of growth of human lung carcinoma cells and induction of apoptosis by a novel phenoxazinone, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one.
Anti-tumor effects of a novel phenoxazinone, 2-amino-4,4-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reaction of 2-amino-5-methylphenol with bovine hemoglobin, were studied in terms of suppression of the proliferation of human lung carcinoma cells and apoptosis induction. When Phx was added to cultures of the human lung carcinoma cell lines A549 (adenocarcinoma) and H226 (squamous carcinoma), it caused the growth inhibition and the death of these cells. Phx also fragmented the DNA of these cells to oligonucleosomal-sized fragments, which is characteristic of the apoptosis, dependent on the dose and exposure time. The cellular death caused by the administration of Phx was partially reversed by the addition of Z-VAD-fmk, a caspase family inhibitor. Present results suggest that Phx demonstrates anti-cancer activity against human lung carcinoma cell lines A549 and H226, by inhibiting growth and inducing apoptosis.
Abe
A
A
Department of Biochemistry, Tokyo Medical University, Shinjuku 6-1-1, Shinjuku-ku, Tokyo 160-0022, Japan.
Yamane
M
M
Tomoda
A
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D061945:Caspase Inhibitors; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010078:Oxazines / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
C104202:2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D010078:Oxazines