Lemons are the third most important Citrus species in production after orange and mandarin in the world. Lemons contain several important naturally occurring chemical components, including phenolics, vitamins, minerals, dietary fiber, essential oils, and limonoids. Obacunone is one of the non-bitter limonoids isolated from lemon seed. In this study, obacunone and obacunone glucoside were isolated using column chromatography and characterized by HPLC, LC-MS, and 2D NMR spectroscopic techniques. To investigate the mechanism of anti-cancer and anti-aromatase activities of limonoids, cytotoxic effect of limonoids on human breast cancer (MCF-7) and non-malignant (MCF-12F) cells was tested. Treatment with obacunone resulted in increased apoptotic effect through up-regulated expression of tumor suppressor p53, pro-apoptotic protein Bax, and down-regulated anti-apoptotic protein Bcl2, as well as induced G1 cell cycle arrest. In addition, obacunone was exhibited significant aromatase inhibition activity in vitro. Down-regulated expression of inflammatory molecules including nuclear factor-kappa B (NF-?B) and cyclooxygenase-2 (COX-2) was also observed in obacunone-treated MCF-7 cells. The down-regulated protein expression of NF- ?B and COX-2 was associated with inhibition of the p38 mitogen-activated protein kinase (MAPK) activity. Finally, uptake of obacunone into the cells were analyzed by HPLC and confirmed by LC-MS analysis. This study demonstrated for the first time that obacunone may have potential in reducing  risk of estrogen-responsive breast cancer through inhibition of the aromatase enzyme activity and inflammatory pathways, as well as activation of apoptosis. The present research report is based on work supported by the �Designing Foods for Health� through USDA CSREES Grant # 2010-34402-20875.

Antiproliferative activity and uptake of obacunone in MCF-7 human breast adenocarcinoma cells

243rd National Meeting (2012)

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