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Obacunone Exhibits Anti-Proliferative and Anti-Aromatase Activity in Vitro by Inhibiting the p38 MAPK Signaling Pathway in MCF-7 Human Breast Adenocarcinoma Cells

Obacunone Exhibits Anti-Proliferative and Anti-Aromatase Activity in Vitro by Inhibiting the p38 MAPK Signaling Pathway in MCF-7 Human Breast Adenocarcinoma Cells

Jinhee Kim, G K Jayaprakasha, Bhimanagouda S Patil

Biochimie. 2014 Oct;105:36-44.

PMID: 24927687

Abstract:

Overexpression of the aromatase enzyme CYP19 has been implicated in the onset of estrogen-dependent breast carcinogenesis. Obacunone, a natural compound present in citrus fruits, has been demonstrated for various biological activities including anti-cancer and anti-inflammatory properties. In the present study, we have isolated obacunone and obacunone glucoside (OG) from lemon seeds, then fractionated these compounds using chromatographic techniques and characterized them by HPLC, LC-MS, and 2D NMR spectral analysis. To investigate the mechanism of anti-cancer and anti-aromatase activities of limonoids, their cytotoxic effect was tested on human breast cancer (MCF-7) and non-malignant (MCF-12F) breast cells. MTT assays confirmed that obacunone was strongly inhibited MCF-7 cell proliferation without affecting non-malignant breast cells. Treatment with obacunone increased apoptosis by up-regulating expression of the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl2, as well as inducing G1 cell cycle arrest. In addition, obacunone significantly inhibited aromatase activity in an in vitro enzyme assay. Exposure of MCF-7 breast cancer cells to obacunone down-regulated expression of inflammatory molecules including nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (COX-2). Furthermore, we found that obacunone inhibited COX-2 and NF-κB by activation of the p38 mitogen-activated protein kinase (MAPK). Finally, the uptake level of obacunone into MCF-7 cells was measured by HPLC and its structure was confirmed by LC-HR-MS. This study demonstrated that obacunone may have the potential to prevent estrogen-responsive breast cancer through inhibition of the aromatase enzyme and inflammatory pathways, as well as activation of apoptosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP751031	Obacunone		751-03-1	Price

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