PMID- 26282490
OWN - NLM
STAT- MEDLINE
DCOM- 20160315
LR  - 20211203
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 240
DP  - 2015 Oct 5
TI  - Dihydrotanshinone I inhibits the translational expression of hypoxia-inducible 
      factor-1alpha.
PG  - 48-58
LID - S0009-2797(15)30035-1 [pii]
LID - 10.1016/j.cbi.2015.08.006 [doi]
AB  - The hypoxia-inducible factor-1 (HIF-1) has been known to be correlated to the 
      adaptation and proliferation of tumor cells; therefore HIF-1 has become an 
      important target in the development of anticancer drugs. Dihydrotanshinone I 
      (DHTS) is a phenanthrenequinone compound from Salvia miltiorrhiza Bunge, which 
      has been used in oriental medicine for its antitumor activities. However, the 
      mechanisms by which DHTS inhibits tumor growth are not fully understood. We here 
      demonstrated the effect of DHTS on hypoxia-inducible factor-1 (HIF-1) activation. 
      DHTS dose-dependently decreased the hypoxia-induced accumulation and activation 
      of HIF-1alpha protein. Further analysis revealed that DHTS inhibited HIF-1alpha protein 
      synthesis, without affecting the expression level of HIF-1alpha mRNA or degradation 
      of HIF-1alpha protein. Moreover, the phosphorylation levels of mammalian target of 
      rapamycin (mTOR), extracellular signal-regulated kinase-1/2 (ERK1/2), ribosomal 
      protein S6 kinase (p70S6K), eIF4E binding protein-1 (4E-BP1), and eukaryotic 
      initiation factor 4E (eIF4E) were dose-dependently suppressed by DHTS, but no 
      significant effect on total protein levels was observed. Furthermore, DHTS 
      prevented hypoxia-induced expression of HIF-1 target genes and flow cytometric 
      analysis indicated that DHTS induced G1 phase arrest in HeLa cell. In vivo 
      studies further confirmed the inhibitory effect of DHTS on the expression of 
      HIF-1alpha proteins, leading to a decrease in growth of HeLa cells in a xenograft 
      tumor model. These results show that DHTS inhibited HIF-1alpha protein synthesis by 
      downregulating the mTOR/p70S6K/4E-BP1 and MEK/ERK pathways. These conclusions 
      suggest that DHTS is an effective inhibitor of HIF-1 and provide new perspectives 
      into the mechanism of its anticancer activity.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Li, Jing
AU  - Li J
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, Department of Chemistry, College of Pharmacy, Molecular 
      Medicine Research Center, Yanbian University, Yanji 133002, Jilin Province, 
      China.
FAU - Mi, Chunliu
AU  - Mi C
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, Department of Chemistry, College of Pharmacy, Molecular 
      Medicine Research Center, Yanbian University, Yanji 133002, Jilin Province, 
      China.
FAU - Ma, Juan
AU  - Ma J
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, Department of Chemistry, College of Pharmacy, Molecular 
      Medicine Research Center, Yanbian University, Yanji 133002, Jilin Province, 
      China.
FAU - Wang, Ke Si
AU  - Wang KS
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, Department of Chemistry, College of Pharmacy, Molecular 
      Medicine Research Center, Yanbian University, Yanji 133002, Jilin Province, 
      China.
FAU - Lee, Jung Joon
AU  - Lee JJ
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, Department of Chemistry, College of Pharmacy, Molecular 
      Medicine Research Center, Yanbian University, Yanji 133002, Jilin Province, 
      China.
FAU - Jin, Xuejun
AU  - Jin X
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, Department of Chemistry, College of Pharmacy, Molecular 
      Medicine Research Center, Yanbian University, Yanji 133002, Jilin Province, 
      China. Electronic address: xjjin@ybu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150814
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Furans)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Phenanthrenes)
RN  - 0 (Quinones)
RN  - 562G9360V6 (dihydrotanshinone I)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Cell Proliferation/drug effects
MH  - Furans
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & 
      inhibitors/*genetics/metabolism
MH  - Phenanthrenes/*pharmacology
MH  - Polymerase Chain Reaction
MH  - Quinones
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Anticancer
OT  - Dihydrotanshinone I (DHTS)
OT  - ERK1/2
OT  - HIF-1
OT  - mTOR
EDAT- 2015/08/19 06:00
MHDA- 2016/03/16 06:00
CRDT- 2015/08/19 06:00
PHST- 2015/04/30 00:00 [received]
PHST- 2015/07/07 00:00 [revised]
PHST- 2015/08/10 00:00 [accepted]
PHST- 2015/08/19 06:00 [entrez]
PHST- 2015/08/19 06:00 [pubmed]
PHST- 2016/03/16 06:00 [medline]
AID - S0009-2797(15)30035-1 [pii]
AID - 10.1016/j.cbi.2015.08.006 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2015 Oct 5;240:48-58. doi: 10.1016/j.cbi.2015.08.006. Epub 
      2015 Aug 14.