PMID- 29152137
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 50
DP  - 2017 Oct 20
TI  - Emodin and rhein decrease levels of hypoxia-inducible factor-1alpha in human 
      pancreatic cancer cells and attenuate cancer cachexia in athymic mice carrying 
      these cells.
PG  - 88008-88020
LID - 10.18632/oncotarget.21330 [doi]
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) consists of 
      oxygen-sensitive HIF-1alpha and constitutive HIF-1beta. HIF-1alpha is undetectable in normal 
      cells, but cancer cells frequently express HIF-1alpha to support their growth, 
      angiogenesis, and high glycolysis (also known as the Warburg effect). The Warburg 
      effect in cancer cells increases energy expenditure and thus participates in 
      cancer-induced metabolic disorder, cancer cachexia. In the present study, we 
      investigated whether two components of Rheum palmatum, emodin and rhein, 
      inhibited HIF-1alpha expression in human pancreatic cancer cells and whether the 
      inhibiting effect, if any, attenuated cancer cachexia. Using Western blotting, we 
      demonstrated that emodin and rhein decreased HIF-1alpha expression in MiaPaCa2 and 
      four other human pancreatic cancer cell lines. We also examined HIF-1alpha expression 
      when MiaPaCa2 cells were exposed to PX-478, noscapine, and phenethyl 
      isothiocyanate, as these compounds were known to inhibit HIF-1alpha expression in 
      different cancer cells. PX-478 and noscapine inhibited HIF-1alpha expression to a 
      less extent than emodin and rhein, and phenethyl isothiocyanate did not inhibit 
      HIF-1alpha expression in tested concentrations. We obtained evidence that emodin and 
      rhein decreased HIF-1alpha by decreasing its biosynthesis but not gene transcription 
      or protein stability. When MiaPaCa2 cells were implanted in athymic mice, emodin 
      and rhein inhibited cancer-cell growth and HIF-1alpha expression. In these athymic 
      mice, emodin and rhein also attenuated two pathological constituents of cancer 
      cachexia, namely high hepatic gluconeogenesis and skeletal-muscle proteolysis. In 
      conclusion, emodin and rhein decrease pancreatic cancer cell's growth and HIF-1alpha 
      expression and attenuate cancer cachexia in the athymic mice carrying the cancer 
      cells.
FAU - Hu, Lijuan
AU  - Hu L
AD  - The Graduate School, Tianjin Medical University, Tianjin, China.
AD  - The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin, China.
FAU - Cui, Rui
AU  - Cui R
AD  - The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin, China.
FAU - Liu, Hongyi
AU  - Liu H
AD  - The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin, China.
FAU - Wang, Feng
AU  - Wang F
AD  - The Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai 
      Hospital, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20170927
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5675689
OTO - NOTNLM
OT  - cachexia
OT  - emodin
OT  - hypoxia-inducible factor-1alpha
OT  - pancreatic cancer
OT  - rhein
COIS- CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.
EDAT- 2017/11/21 06:00
MHDA- 2017/11/21 06:01
PMCR- 2017/10/20
CRDT- 2017/11/21 06:00
PHST- 2017/08/01 00:00 [received]
PHST- 2017/08/28 00:00 [accepted]
PHST- 2017/11/21 06:00 [entrez]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2017/11/21 06:01 [medline]
PHST- 2017/10/20 00:00 [pmc-release]
AID - 21330 [pii]
AID - 10.18632/oncotarget.21330 [doi]
PST - epublish
SO  - Oncotarget. 2017 Sep 27;8(50):88008-88020. doi: 10.18632/oncotarget.21330. 
      eCollection 2017 Oct 20.