PMID- 30966770
OWN - NLM
STAT- MEDLINE
DCOM- 20191017
LR  - 20201209
IS  - 1793-6853 (Electronic)
IS  - 0192-415X (Linking)
VI  - 47
IP  - 3
DP  - 2019
TI  - beta-Pentagalloyl-Glucose Sabotages Pancreatic Cancer Cells and Ameliorates Cachexia 
      in Tumor-Bearing Mice.
PG  - 675-689
LID - 10.1142/S0192415X19500356 [doi]
AB  - Pancreatic cancer cells overexpress the insulin receptor (IR) and the 
      insulin-like growth factor-1 receptor (IGF1R). Activating these receptors, 
      insulin and insulin-like growth factor-1 increase the growth and glycolysis of 
      pancreatic cancer cells. The high glycolysis in pancreatic cancer cells increases 
      whole-body energy expenditure and is therefore involved in the pathogenesis of 
      cancer cachexia. The antagonism of IR and IGF1R may sabotage pancreatic cancer 
      cells and attenuate cancer cachexia. Previous studies have shown that the 
      intracellular regulating system of IR/IGF1R may be functionally interrelated to 
      another intracellular system whose master regulator is hypoxia-inducible factor-1 
      (HIF-1). In this study, we investigated how the IR/IGF1R and HIF-1 systems are 
      interrelated in pancreatic cancer cells. We also investigated whether a 
      phytochemical, penta-O-galloyl- beta -D-glucose ( beta -PGG), antagonizes IR/IGF1R, 
      sabotages pancreatic cancer cells and alleviates cancer cachexia. We found in 
      MiaPaCa2 pancreatic cancer cells that IR/IGF1R activation increased both the alpha 
      -subunit of HIF-1 and caveolin-1. This result suggests that IR/IGF1R, HIF-1 alpha , 
      and caveolin-1 may constitute a feed-forward loop to mediate the effect of 
      IR/IGF1R activation. beta -PGG inhibited IR/IGF1R activity and decreased glycolytic 
      enzymes in MiaPaCa2 and Panc-1 pancreatic cancer cells. When MiaPaCa2 cells were 
      transplanted in athymic mice, their growth was inhibited by beta -PGG or by a HIF-1 
      alpha inhibitor, rhein. beta -PGG and rhein also decreased glycolytic enzymes in the 
      tumor grafts and reduced liver gluconeogenesis, skeletal-muscle proteolysis and 
      fat lipolysis in the tumor carriers. Cancer-induced body-weight loss, however, 
      was prevented by beta -PGG but not rhein. In conclusion, beta -PGG combats pancreatic 
      cancer cells and cures cancer cachexia.
FAU - Yang, Jing
AU  - Yang J
AD  - * The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China.
AD  - dagger The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin 300100, P. R. China.
FAU - Wang, Feng
AU  - Wang F
AD  - dagger The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin 300100, P. R. China.
FAU - Chen, Xijuan
AU  - Chen X
AD  - * The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China.
AD  - dagger The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin 300100, P. R. China.
FAU - Qiu, Shuai
AU  - Qiu S
AD  - * The Graduate School, Tianjin Medical University, Tianjin 300070, P. R. China.
AD  - dagger The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin 300100, P. R. China.
FAU - Cui, Lihua
AU  - Cui L
AD  - dagger The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin 300100, P. R. China.
FAU - Hu, Lijuan
AU  - Hu L
AD  - dagger The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin 300100, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20190409
PL  - Singapore
TA  - Am J Chin Med
JT  - The American journal of Chinese medicine
JID - 7901431
RN  - 0 (Cav1 protein, mouse)
RN  - 0 (Caveolin 1)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hydrolyzable Tannins)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (IGF1R protein, human)
RN  - 0 (Receptors, Somatomedin)
RN  - 3UI3K8W93I (pentagalloylglucose)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Cachexia/*drug therapy/etiology
MH  - Caveolin 1/metabolism
MH  - Glycolysis
MH  - Humans
MH  - Hydrolyzable Tannins/*pharmacology/*therapeutic use
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Neoplasm Transplantation
MH  - Pancreatic Neoplasms/complications/*metabolism
MH  - Receptor, IGF Type 1
MH  - Receptor, Insulin/antagonists & inhibitors/metabolism
MH  - Receptors, Somatomedin/antagonists & inhibitors/metabolism
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Cachexia
OT  - Caveolin-1
OT  - Hypoxia-Inducible Factor-1
OT  - Pancreatic Cancer
OT  - Penta-O-Galloyl-beta-D-Glucose
OT  - The Insulin Receptor
EDAT- 2019/04/11 06:00
MHDA- 2019/10/18 06:00
CRDT- 2019/04/11 06:00
PHST- 2019/04/11 06:00 [pubmed]
PHST- 2019/10/18 06:00 [medline]
PHST- 2019/04/11 06:00 [entrez]
AID - 10.1142/S0192415X19500356 [doi]
PST - ppublish
SO  - Am J Chin Med. 2019;47(3):675-689. doi: 10.1142/S0192415X19500356. Epub 2019 Apr 
      9.