Tea polyphenol epigallocatechin-3-gallate inhibits cell proliferation in a patient-derived triple-negative breast cancer xenograft mouse model via inhibition of proline-dehydrogenase-induced effects

Wen Jui Lee, Tzu Chun Cheng, Yun Yen, Chia Lang Fang, You Cheng Liao, Ching Chuan Kuo, Shih Hsin Tu, Li Cheng Lin, Hui Wen Chang, Li Ching Chen, Yuan Soon Ho

研究成果: 雜誌貢獻文章同行評審

摘要

Triple-negative breast cancers (TNBCs) lack specific targeted therapy options and have evolved into highly chemo-resistant tumors that metastasize to multiple organs. The present study demonstrated that the proline dehydrogenase (PRODH) mRNA level in paired (tumor vs. normal) human breast tissue samples (n ¼ 234) was 6.6-fold greater than normal cells (*p ¼ 0.021). We established stable PRODH-overexpressing TNBC (HS578T) cells, and the malignant phenotypes were evaluated using soft agar colony formation and Transwell migration assays. The results demonstrated that PRODH induced epithelial-mesenchymal transition in cancer cells and increased cell proliferation. The present study found that the tea polyphenol epigallocatechin-3-gallate (EGCG) significantly inhibited PRODH and its regulated proteins, such as alpha-smooth muscle actin (alpha-SMA) expression in TNBC cells. These findings support the targeting of the PRODH signaling pathway as a potential therapeutic strategy in preventing cancer cell metastasis. The patient-derived xenograft (PDX) mouse model is highly relevant to real human tumor growth. We established a TNBC-PDX (F4, n ¼ 4 in each group) mouse model. The PDX mice were treated with EGCG (50 mg/kg), and the results indicated that EGCG significantly inhibited PDX tumor growth (*p ¼ 0.013). These experiments provide additional evidence to evaluate the antitumor effects of EGCG-induced PRODH inhibition for clinical therapeutic application, especially in TNBC patients.
原文英語
文章編號9
頁(從 - 到)113-127
頁數15
期刊Journal of Food and Drug Analysis
29
發行號1
DOIs
出版狀態已發佈 - 2021

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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