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

Abstract

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.

Involvement of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2-aminophenoxazine-3-one in cancer cells

“…Morphological studies of the cells after treatment with Phx-3 indicated typical features of apoptosis (e.g. chromatin condensation and nuclear fragments), as previously reported (data not shown) (5,6). Although cell growth inhibition was detected in all cell lines, A549 lung adenocarcinoma cells exhibited the most potent growth inhibition in response to Phx-3.…”

2-Aminophenoxazine-3-one Suppresses the Growth of Mouse Malignant Melanoma B16 Cells Transplanted into C57BL/6Cr Slc Mice

“…This result is comparable to our previous report on the anticancer activity of Phx-3 against human malignant melanoma G361 cells 11) and on that of Phx-1 against various cancer cell lines. [6][7][8][9][10] We furthermore demonstrated that the growth of mouse malignant melanoma B16 cells transplanted into C57BL/6Cr Slc mice was completely inhibited by the administration of 0.5 mg/kg Phx-3 (Figs. 3, 4).…”

Synergistic enhancement of TRAIL- and tumor necrosis factor α–induced cell death by a phenoxazine derivative

“…Phx-1 is produced by the reaction of 2-amino-5-methylphenol with human or bovine hemoglobin. Phx-1 inhibits the proliferation of a variety of cultured cell lines such as human epidermoid carcinoma cells (8), Meth A tumor cells (9), human lung carcinoma cell lines (10), leukemia cell lines K562, HL-60, and HAL-01 (11), human endometrial adenocarcinoma cell lines EN and KLE cells (12). In addition to the in vitro effects, Phx-1 also reduces the growth of tumor cells in mice that are transplanted with the cells (9,11).…”