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Nutrition and Cancer

Green Tea Inhibits Vascular Endothelial Growth Factor (VEGF) Induction in Human Breast Cancer Cells

Maryam R. Sartippour, Zhi-Ming Shao, David Heber^*, Perrin Beatty, Liping Zhang, Canhui Liu, Lee Ellis, Wen Liu, Vay Liang Go^* and Mai N. Brooks³

Department of Surgery, Division of Oncology and ^* Center for Human Nutrition, University of California, Los Angeles, CA and University of Texas, MD Anderson Cancer Center, Houston, TX^{1 ,2}

³To whom correspondence should be addressed. E-mail: mainguyen{at}mednet.ucla.edu.

Investigators have shown that green tea and its main catechin epigallocatechin-3 gallate (EGCG) may decrease the risk of cancer. Our previous study showed that green tea extract (GTE) as well as its individual catechin components inhibited MDA-MB231 breast cancer cell and human umbilical vein endothelial cell (HUVEC) proliferation. Further, GTE suppressed breast cancer xenograft size and decreased the tumor vessel density in vivo. In the current study, we investigated the effect of GTE on the major angiogenic factor vascular endothelial growth factor (VEGF) in an in vitro experiment. GTE or EGCG (40 mg/L) significantly decreased the levels of the VEGF peptide secreted into conditioned media. This occurred in both HUVEC and human breast cancer cells and the effect was dose dependent. Furthermore, GTE and EGCG decreased the RNA levels of VEGF in MDA-MB231 cells. This inhibition occurred at the transcriptional regulation level and was accompanied by a significant decrease in VEGF promoter activity. We also showed that GTE decreased c-fos and c-jun RNA transcripts, suggesting that activator protein (AP)-1–responsive regions present in the human VEGF promoter may be involved in the inhibitory effect of GTE. Furthermore, GTE suppressed the expression of protein kinase C, another VEGF transcription modulator, in breast cancer cells. Inhibition of VEGF transcription appeared to be one of the molecular mechanism(s) involved in the antiangiogenic effects of green tea, which may contribute to its potential use for breast cancer treatment and/or prevention.

KEY WORDS: • green tea • vascular endothelial growth factor • epigallocatechin-3 gallate • breast cancer • angiogenesis

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