PMID- 30310905
OWN - NLM
STAT- MEDLINE
DCOM- 20190329
LR  - 20211020
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Print)
IS  - 2042-6496 (Linking)
VI  - 9
IP  - 11
DP  - 2018 Nov 14
TI  - Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces 
      breast cancer cell growth in preclinical models.
PG  - 5682-5696
LID - 10.1039/c8fo01397g [doi]
AB  - 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 muM) 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 1alpha (HIF1alpha) 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.
FAU - Wei, Ran
AU  - Wei R
AD  - Institute of Tea Science, Zhejiang University, Hangzhou, Zhejiang 310058, China. 
      zdcy@zju.edu.cn.
FAU - Mao, Limin
AU  - Mao L
FAU - Xu, Ping
AU  - Xu P
FAU - Zheng, Xinghai
AU  - Zheng X
FAU - Hackman, Robert M
AU  - Hackman RM
FAU - Mackenzie, Gerardo G
AU  - Mackenzie GG
FAU - Wang, Yuefei
AU  - Wang Y
LA  - eng
GR  - P30 CA093373/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Atg5 protein, mouse)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Beclin-1)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Polyphenols)
RN  - 0 (Slc2a1 protein, mouse)
RN  - 0 (Tea)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp8 protein, mouse)
RN  - EC 3.4.22.- (Casp9 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Autophagy-Related Protein 5/genetics/metabolism
MH  - Beclin-1/genetics/metabolism
MH  - Breast Neoplasms/*drug therapy
MH  - Caspase 3/genetics/metabolism
MH  - Caspase 8/genetics/metabolism
MH  - Caspase 9/genetics/metabolism
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Cell Survival/drug effects
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 1/genetics/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Polyphenols/pharmacology
MH  - Tea/chemistry
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC7480214
MID - NIHMS1626197
COIS- Conflicts of interest There are no conflicts to declare.
EDAT- 2018/10/13 06:00
MHDA- 2019/03/30 06:00
PMCR- 2020/09/09
CRDT- 2018/10/13 06:00
PHST- 2018/10/13 06:00 [pubmed]
PHST- 2019/03/30 06:00 [medline]
PHST- 2018/10/13 06:00 [entrez]
PHST- 2020/09/09 00:00 [pmc-release]
AID - 10.1039/c8fo01397g [doi]
PST - ppublish
SO  - Food Funct. 2018 Nov 14;9(11):5682-5696. doi: 10.1039/c8fo01397g.