Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models

Ran Wei, Limin Mao, Ping Xu, Xinghai Zheng, Robert M. Hackman, Gerardo Mackenzie, Yuefei Wang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Numerous studies propose that epigallocatechin-3-gallate (EGCG), an abundant polyphenol in green tea, has anti-cancer properties. However, its mechanism of action in breast cancer remains unclear. This study investigated the capacity of EGCG to suppress breast cancer cell growth in vitro and in vivo, characterizing the underlying mechanisms, focusing on the effect of EGCG on glucose metabolism. EGCG reduced breast cancer 4T1 cell growth in a concentration- (10-320 μM) and time- (12-48 h) dependent manner. EGCG induced breast cancer apoptotic cell death at 24 h, as evidenced by annexin V/PI, caspase 3, caspase 8 and caspase 9 activation. Furthermore, EGCG affected the expression of 16 apoptosis-related genes, and promoted mitochondrial depolarization. EGCG induced autophagy concentration-dependently in 4T1 cells by modulating the levels of the autophagy-related proteins Beclin1, ATG5 and LC3B. Moreover, EGCG affected glucose, lactate and ATP levels. Mechanistically, EGCG significantly inhibited the activities and mRNA levels of the glycolytic enzymes hexokinase (HK), phosphofructokinase (PFK), and lactic dehydrogenase (LDH), and to a lesser extent the activity of pyruvate kinase (PK). In addition, EGCG decreased the expression of hypoxia-inducible factor 1α (HIF1α) and glucose transporter 1 (GLUT1), critical players in regulating glycolysis. In vivo, EGCG reduced breast tumor weight in a dose-dependent manner, reduced glucose and lactic acid levels and reduced the expression of the vascular endothelial growth factor (VEGF). In conclusion, EGCG exerts an anti-tumor effect through the inhibition of key enzymes that participate in the glycolytic pathway and the suppression of glucose metabolism.

Original languageEnglish (US)
Pages (from-to)5682-5696
Number of pages15
JournalFood and Function
Volume9
Issue number11
DOIs
StatePublished - Nov 1 2018

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epigallocatechin
growth models
breast neoplasms
cell growth
Breast Neoplasms
Glucose
glucose
metabolism
Growth
autophagy
glycolysis
neoplasm cells
epigallocatechin gallate
Lactic Acid
caspase-8
Hypoxia-Inducible Factor 1
caspase-9
Phosphofructokinases
phosphofructokinases
glucose transporters

ASJC Scopus subject areas

  • Food Science

Cite this

Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models. / Wei, Ran; Mao, Limin; Xu, Ping; Zheng, Xinghai; Hackman, Robert M.; Mackenzie, Gerardo; Wang, Yuefei.

In: Food and Function, Vol. 9, No. 11, 01.11.2018, p. 5682-5696.

Research output: Contribution to journalArticle

Wei, Ran ; Mao, Limin ; Xu, Ping ; Zheng, Xinghai ; Hackman, Robert M. ; Mackenzie, Gerardo ; Wang, Yuefei. / Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models. In: Food and Function. 2018 ; Vol. 9, No. 11. pp. 5682-5696.
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