Mechanisms of action for green tea extract in breast cancer prevention identified

October 18, 2012

An oral green tea extract, Polyphenon E, appears to inhibit vascular endothelial growth factor and hepatocyte growth factor, both of which promote tumor cell growth, migration and invasion.

Researchers made this discovery during a secondary analysis of a phase Ib randomized, placebo-controlled study of Polyphenon E in a group of 40 women with hormone receptor-negative . Katherine D. Crew, M.D., assistant professor of medicine and epidemiology at Columbia University Medical Center in New York, N.Y., presented the data at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 16-19, 2012.

"Many have looked at epigallocatechin-3-gallate, or , which is one of the main components of green tea, and the various possible mechanisms of its action against cancer, but it is very difficult to do those same kinds of studies in humans," Crew said. "This study was too small to say for sure if green tea will prevent breast cancer, but it may move us forward in terms of understanding antitumor mechanisms."

In the primary analysis, presented at last year's Frontiers in meeting, 40 women were randomly assigned to 400 mg, 600 mg or 800 mg of Polyphenon E or to placebo twice daily for six months. During that time, researchers collected blood and urine samples from participants at baseline and at two, four and six months.

In this secondary analysis, Crew and colleagues used the blood and urine samples to examine biologic endpoints, such as , growth factors and lipid biomarkers, which might point to the mechanism of action behind . Biomarker data were available for 34 of the 40 patients.

Women assigned to the extract had an average 10-fold increase in green tea metabolites compared with placebo. In addition, they had a significant reduction in hepatocyte growth factor levels at two months compared with women assigned to placebo. However, at the four-month and six-month follow-ups, the difference was no longer statistically significant.

The researchers also identified a trend toward decreased total serum cholesterol and decreased vascular endothelial growth factor in women assigned to the extract.

According to Crew, it is still too early to recommend green tea extract to prevent breast cancer. Currently, researchers are conducting several ongoing studies to explore the use of oral extract in high-risk women for the primary prevention of breast cancer.

Explore further: Tea epigallocatechin-3-gallate inhibits cell proliferation in breast cancer patients

More information: A73 Evaluating tissue biomarker effects of an oral green tea extract, Polyphenon E, using reverse phase protein array in women with operable breast cancer. Kimberly A. Ho et al.

Abstract
Background: Numerous epidemiologic studies and experimental data support potential anti-tumor effects of green tea and its main component, epigallocatechin-3-gallate (EGCG), in breast cancer. However, there is limited data on the effects of tea catechins on breast cancer in human intervention trials. The purpose of this study is to evaluate tumor proteomic changes after short-term pre-surgical administration of an oral green tea extract, Polyphenon E (Poly E), in women with operable breast cancer using reverse phase protein array (RPPA).

Methods: This is a phase II single-arm open-label trial of oral Poly E 800 mg daily for 2-4 weeks in women with histologically-confirmed breast cancer on core biopsy who were scheduled for surgical resection. Formalin-fixed paraffin-embedded (FFPE) tumor tissue from the diagnostic core biopsy (pre-treatment) and surgical resection (post-treatment) were analyzed for expression of the Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PR), and HER2 by immunohistochemistry (IHC). Protein was extracted for RPPA analysis of 161 proteins, including components of the PI3K/AKT and MAPK pathways. Women were matched by age, breast cancer stage, ER/PR/HER2 status, and time interval between breast biopsy and surgery to untreated historical controls. Paired t-test was used to calculate changes in protein markers before and after Poly E treatment and 2-sample t-test to compare biomarker changes in the treatment and no treatment groups. All statistical analyses were 2-sided and performed using SAS version 9.1.

Results: From Feb 2008 to Sept 2009, 25 women were enrolled and 21 were evaluable. Median age: 50 years (range, 33-71); White/Hispanic/Black (%): 44/48/7; Stage 0/I/II/III (%): 11/48/30/11; hormone receptor +/- (%): 85/15. Mean duration on Poly E was 20 days (range, 13-36). We demonstrated significant correlations between RPPA and IHC for Ki-67 (0.46, P<0.0001), ER (0.45, P=0.0017), PR (0.46, P=0.0014), and a trend for HER2 (0.28, P=0.0923). Poly E treatment did not cause a significant decrease in Ki-67 compared to untreated controls (mean absolute change, -0.5% vs. +2.6%, P=0.83). In the Poly E-treated group, the RPPA results showed significant modulation of apoptosis and PI3K/AKT pathway proteins (P<0.05). After Bonferroni correction to adjust for multiple comparisons (P<0.00031), 11 markers remained statistically significant comparing change from baseline with Poly E treatment: up-regulation of MEK1, JNK2, and p38-MAPK; down-regulation of CDK4, HER2-pY1248, MAPK-pT202-Y204, MIG-6, mTOR-pS2448, PRAS40-pT246, Src-pY416, and Scr-pY527. Compared to untreated controls, the Poly E group had significant changes from baseline in 10 proteins: up-regulation of IRS1, p38-MAPK, Notch1, and YAP; down-regulation of ERCC1, MIG-6, p90RSK-pT359-S363, PRAS40-pT246, Smad3, and Src-pY416 (P<0.05).

Conclusions: Short-term administration of Poly E did not significantly decrease proliferation in breast tumor tissue; however, our RPPA data suggests that Poly E may act on alternative signaling pathways. The changes we observed in CDK4, HER2, Src, MAPK, and JNK expression are consistent with preclinical studies of EGCG. This is one of the first human intervention trials to demonstrate the biologic effects of Poly E on growth factor signaling pathways in breast cancer.

Related Stories

Tea epigallocatechin-3-gallate inhibits cell proliferation in breast cancer patients

October 21, 2011
(Medical Xpress) -- Erxi Wu, assistant professor of pharmaceutical sciences, and Fengfei Wang, research associate of pharmaceutical sciences, co-wrote the article, "Anti-cancer activities of tea epigallocatechin-3-gallate ...

Recommended for you

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

How CD44s gives brain cancer a survival advantage

July 19, 2017
Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure the disease. In the case of glioblastoma multiforme, the deadliest ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.