Anti-Cancer Activities of Tea Epigallocatechin-3-Gallate in Breast Cancer Patients under Radiotherapy

Abstract

The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment with radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radiotherapy alone, those given radiotherapy plus EGCG for an extended time period (two to eight weeks) showed significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 and metalloproteinase-2 (MMP9/MMP2). Addition of sera obtained from patients treated with combination of radiotherapy and EGCG feeding for 2–8 weeks to in vitro cultures of highly-metastatic human MDA-MB-231 breast cancer cells resulted in the following significant changes: (1) suppression of cell proliferation and invasion; (2) arrest of cell cycles at the G0/G1 phase; (3) reduction of activation of MMP9/MMP2, expressions of Bcl-2/Bax, c-Met receptor, NF-κB, and the phosphorylation of Akt. MDA-MB-231 cells exposed to 5–10 µM EGCG also showed significant augmentation of the apoptosis inducing effects of γ-radiation, concomitant with reduced NF-κB protein level and AKT phosphorylation. These results provide hitherto unreported evidence that EGCG potentiated efficacy of radiotherapy in breast cancer patients, and raise the possibility that this tea polyphenol has potential to be a therapeutic adjuvant against human metastatic breast cancer.

Suppression of proliferation and migration in highly-metastatic lung cancer cells as well as tumor growth by a new synthesized compound TBrC and its molecular mechanisms of action

“…Activation of p-Akt and the NF-jB/Bcl-2 pathway leads to inhibition of chemotherapy-induced apoptosis, which results in treatment resistance (Wang et al 1996). Our previous results confirmed that suppression of Akt and the NF-jB/Bcl-2 pathway by anticancer agents inhibited the growth and migration as well as induced apoptosis and cell cycle arrest in human lung cancer A549 cells and breast cancer MDA-MB-231 cells Wang et al 2009;Yu et al 2009;Jiang et al 2010;Zhang et al 2012a). In the present study, we indicated that TBrC significantly enhanced the inhibition of the proliferation and migration of LLC cells and the PI3K/Akt and NF-jB pathway by suppressing the phosphorylation and expression of Akt and the NF-jB expression and activating the apoptotic pathway related to changes of Bcl-2/Bax ratio, mitochondrial cytochrome C and caspase-3 in LLC cells.…”

“…These were done according to our published methods (Wang et al 2009;Yu et al 2009;Zhang et al 2000Zhang et al , 2012a. In brief, LLC cells were treated for 48 h with TBrC ( .…”

“…This was performed according to our published methods with some modifications (Wang et al 2009;Yu et al 2009;Zhang et al 2009, Jiang et al 2010Zhang et al 2012a). In brief, LLC cells were treated with different concentrations of TBrC (16-250 microM), theanine (16-250 microM), Ly294002 (Ly, 16 microM), or Bay (3.2 microM).…”

Enhanced suppression of proliferation and migration in highly-metastatic lung cancer cells by combination of valproic acid and coumarin-3-carboxylic acid and its molecular mechanisms of action

“…Flow cytometry for cell cycle analysis and apoptosis These were done according to our published methods (Wang et al 2009;Yu et al 2009;Zhang et al 2000Zhang et al , 2012a. In brief, LLC cells were treated for 48 h with sodium valproate (VPA, 0.5 mM), coumarin-3-carboxylic acid (HCCA, 0.064 mM), or in combination of VPA (0.5 mM) and HCCA (0.064 mM).…”

“…This was performed according to our published methods with some modifications (Wang et al 2009;Yu et al 2009;Zhang et al 2009Zhang et al , 2012aJiang et al 2010). In brief, LLC cells were treated with different concentrations of sodium valproate (VPA, 0.5-1 mM), coumarin-3-carboxylic acid (HCCA, 0.064-0.125 mM), or in combination of VPA and HCCA, or Ly294002 (Ly, 0.0125 mM), Bay (0.0025 mM).…”