MECHANISMS OF ANTITUMOR ACTIVITY BY MELANOXOIN ON HUMAN NON-SMALL CELL LUNG CANCER CELLS
Chieh-Yu Peng1,2, Shou-Fang Wu3, Hsiu-Yi Hung1 and Yang-Chang Wu1,2
1Natural Medicinal Products Research Center and Center for Molecular Medicine, China Medical
University Hospital, Taichung 404, Taiwan 2School of Chinese Medicine, College of Chinese
Medicine, China Medical University, Taichung 404, Taiwan. 3Graduate Institute of Natural Products,
Kaohsiung Medical University, Kaohsiung 807, Taiwan
Cancer is a leading cause of death worldwide. The standard treatments of cancer include surgery, chemotherapy, radiation therapy and the newer targeted therapy. Till now, there are various anticancer drugs, which derived from natural products. In this study, we screened a serious of compounds isolated from Pterocarpus santalinus to identify their cell cytotoxicity. We performed the MTT assay to evaluate the cytotoxic effects of test compounds against several human cancer cell lines. Among them, melanoxoin showed the highest cytotoxic effects with a IC50 of 1.98 µg/ml
in the human non-small cell lung cancer H1299 cells. We next used Human OneArray® v5 to comprehensive analysis the DNA transcription of H1299 cells. It showed that melanoxoin
regulated the transcription of several cell cycle regulators in the H1299 cells. Cell cycle analysis by flow cytometry revealed melanoxoin causes G2/M arrest and then increased tumor cell apoptosis. The neutral comet assay revealed that the treatment with melanoxoin induced significant DNA damage in H1299 cells. Therefore, we are interested in the development the molanoxoin as a new source of anti-cancer drug.
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