title: 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.
authors.affiliation: Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, Yantai, Shandong Province 264005, China. zhang_zhang6173@yahoo.com.cn
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wan
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Qu
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: H
authors.initials: H
authors.lastname: Duan
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Hou
authors.forename: S
authors.initials: S
authors.lastname: Jin
authors.forename: T-C
authors.initials: TC
authors.lastname: Hsieh
authors.forename: E
authors.initials: E
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D013662:Tea; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D017228:Hepatocyte Growth Factor; D002392:Catechin; C045651:epigallocatechin gallate; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9