PMID- 35853845
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20240102
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 42
IP  - 12
DP  - 2022 Dec
TI  - Inhibition of hypoxia-induced HIF-1alpha-mediated autophagy enhances the in vitro 
      antitumor activity of rhein in pancreatic cancer cells.
PG  - 1937-1947
LID - 10.1002/jat.4365 [doi]
AB  - A hypoxic microenvironment results in significantly elevated hypoxia-inducible 
      factor-1 (HIF-1) level in pancreatic cancer. HIF-1 functions to maintain the 
      survival of cancer cells. The present study was performed to investigate whether 
      inhibition of HIF-1alpha expression was involved in the in vitro antitumor effect of 
      rhein in pancreatic cancer cells and to explore the underlying mechanism. sh-RNA 
      knockout technique and western blotting were used to investigate the role of 
      HIF-1alpha in autophagy activation in MiaPaCa-2 and PANC-1 cells. The survival and 
      glycolysis were assessed using MTT assay and colorimetric kits, respectively. 
      Apoptosis was evaluated by detecting the levels of apoptosis-related proteins 
      using western blotting. Among the five pancreatic cancer cell lines, MiaPaCa-2 
      and PANC-1 cells were more sensitive to hypoxia-induced autophagy. HIF-1alpha 
      regulated hypoxia-induced autophagy in MiaPaCa-2 and PANC-1 cells. Treatment with 
      rhein inhibited the survival and suppressed glycolysis in MiaPaCa-2 and PANC-1 
      cells exposed to hypoxia. Bafilomycin A1 enhanced the suppressive effects of 
      rhein on cell survival and glycolysis under hypoxia. Treatment with rhein, but 
      not bafilomycin A1, significantly reduced HIF-1alpha expression. In conclusion, 
      inhibition of HIF-1alpha-mediated autophagy enhances the in vitro antitumor activity 
      of rhein in pancreatic cancer cells under hypoxia.
CI  - (c) 2022 John Wiley & Sons Ltd.
FAU - Yao, Chuanshan
AU  - Yao C
AD  - The Medical School, Nankai University, Tianjin, China.
AD  - Department of Oncology, Nanyang First People's Hospital, Henan, China.
FAU - Wang, Feng
AU  - Wang F
AUID- ORCID: 0000-0003-1051-4438
AD  - The Medical School, Nankai University, Tianjin, China.
AD  - The Laboratory of Acute Abdomen Disease Associated Organ Injury and Repair, 
      Nankai Hospital Affiliated to Nankai University, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20220725
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - YM64C2P6UX (rhein)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Humans
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - *Pancreatic Neoplasms/drug therapy/genetics/metabolism
MH  - Autophagy
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - autophagy
OT  - glycolysis
OT  - hypoxia-inducible factor-1
OT  - pancreatic cancer
OT  - rhein
EDAT- 2022/07/20 06:00
MHDA- 2022/11/15 06:00
CRDT- 2022/07/19 23:03
PHST- 2022/07/12 00:00 [received]
PHST- 2022/07/15 00:00 [accepted]
PHST- 2022/07/20 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/07/19 23:03 [entrez]
AID - 10.1002/jat.4365 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2022 Dec;42(12):1937-1947. doi: 10.1002/jat.4365. Epub 2022 Jul 
      25.