Antiproliferative Activity of Pomiferin in Normal (MCF-10A) and Transformed (MCF-7) Breast Epithelial Cells
2011
Yang, Raymond | Hanwell, Heather | Zhang, Jing | Tsao, Rong | Meckling, Kelly Anne
Pomiferin and osajin are prenylated isoflavones from Osage orange fruit that both have potent antioxidant activity in a variety of assays. Pomiferin, in particular, has strong activity against the superoxide anion in a photochemiluminescence (PCL) assay system. In vitro, pomiferin, but not osajin, demonstrated selective antiproliferative activity against the tumorigenic breast epithelial cell line MCF-7 (IC50 = 5.2 μM) with limited toxicity toward nontumorigenic breast epithelial cells (MCF-10A). The differential sensitivity of normal and tumorigenic cells to the antiproliferative action of pomiferin was examined further by using cDNA microarrays. With a stringent cutoff of p < 0.01, a total of 94 genes were significantly differentially expressed between MCF-7 and MCF-10A cells; 80 up-regulated and 14 down-regulated when cells were exposed to 5 μM pomiferin for 24 h. Fold changes by microarray analysis were confirmed using RT-qPCR, and the most significant changes were found with genes related to antioxidant enzymes. Genes involved in mitotic inhibition and apoptotic regulations were also found to be up-regulated. Pomiferin is therefore a good anticancer candidate agent that may be useful either alone or in combination with other therapeutic agents and, because of its selectivity toward tumor cells, likely to have fewer side effects that classic chemotherapy drugs.
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