Experiments were also performed in a preclinical cell culture model for human ductal breast carcinoma in situ (DCIS). The human breast-derived preneoplastic cell line 184-B5/HER expressed HER-2/neu, p53 and EGFR but not ER, therefore resembling the clinical DCIS. Initial dose-response experiments compared the growth inhibitory effect of orange peel extract on the parental 184-B5 cells and the HER-2/neu oncogene-expressing 184-B5/HER cells. Relative to parental cells, orange peel extract was at least two times more effective as a growth inhibitor for 184-B5/HER cells. Orange peel extract at the maximum cytostatic dose of 100 ppm accumulated the cells in the G0/G1 phase and inhibited the S+G2/M phase of the cell cycle, leading to down-regulation of cell cycle progression. This alteration in the cell cycle progression resulted in a 5-fold increase in the G0/G1: S+G2/M ratio. Treatment of 184-B5/HER cells with 100 ppm orange peel extract resulted in a 47.5% decrease in immunoreactivity to phosphotyrosine (marker for tyrosine kinase activity) and a 157.7% increase in immunoreactivity to the cyclin dependent kinase inhibitor p16
INKA. In addition, there was a selective induction of apoptosis in 184-B5/HER cells but not in parental 184-B5 cells. Treatment of 184-B5/HER cells with 100 ppm orange peel extract induced a 7.6-fold increase in sub G0/G1 (apoptotic) population. Consistent with the induction of apoptosis, immunoreactivity to anti-apoptotic Bcl-2 was decreased by 33%.
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This article suggests combining orange peel extract with other proven anti-tumor foods, such as black tea and grapes.