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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 Effect

【Update Date：2021-04-15】unit：

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 a, Tzu-Chun Cheng b,1, Yun Yen c,d,j,1, Chia-Lang Fang e,f, You-Cheng Liao b, Ching-Chuan Kuo g, Shih-Hsin Tu c,h, Li-Cheng Lin b, Hui-Wen Chang i, Li-Ching Chen c,j,**, Yuan-Soon Ho b,i,j,k,l,*

a Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taiwan

b Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

c Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

d Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan

e Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

f Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

g Associate Investigator, Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Taiwan

h Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

i Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan

j TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan

k School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

l Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan


Triple-negative breast cancers (TNBCs) lack specific targeted therapy options and have evolved into highly chemoresistant tumors that metastasize to multiple organs. The present study demonstrated that the proline dehydrogenase (PRODH)mRNAlevel in paired (tumor vs. normal) human breast tissue samples (n꞊234) was 6.6-fold greater than normal cells (*p꞊0.021).Weestablished 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 PRODHinduced 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 alphasmooth 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꞊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꞊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.

Keywords: Triple-negative breast cancer, Proline dehydrogenase, Epigallocatechin-3-gallate, Patient-derived xenograft

https://doi.org/10.38212/2224-6614.3230

(https://www.jfda-online.com/journal/vol29/iss1/9)