Prevention of growth of human lung carcinoma cells and induction of apoptosis by a novel phenoxazinone, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one

Anti-tumor effects of a novel phenoxazinone, 2-amino-4,4-dihydro- 4 alpha ,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 anticancer activity against human lung carcinoma cell lines A549 end H226, by inhibiting growth and inducing apoptosis. [(C) 2001 Lippincott Williams & Wilkins.].