PMID- 25659153
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 2
DP  - 2015
TI  - Tanshinone IIA inhibits HIF-1alpha and VEGF expression in breast cancer cells via 
      mTOR/p70S6K/RPS6/4E-BP1 signaling pathway.
PG  - e0117440
LID - 10.1371/journal.pone.0117440 [doi]
LID - e0117440
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor 
      (VEGF) play important roles in angiogenesis and tumor growth. Tanshinone IIA 
      (T2A) is a novel antiangiogenic agent with promising antitumor effects; however, 
      the molecular mechanism underlying the antiangiogenic effects of T2A remains 
      unclear. In the present study, we provided evidence showing that T2A inhibited 
      angiogenesis and breast cancer growth by down-regulating VEGF expression. 
      Specifically, T2A repressed HIF-1alpha expression at the translational level and 
      inhibited the transcriptional activity of HIF-1alpha, which led to the 
      down-regulation of VEGF expression. Suppression of HIF-1alpha synthesis by T2A 
      correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) 
      and its effectors ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation 
      factor 4E-binding protein-1 (4E-BP1), a pathway regulating HIF-1alpha expression at 
      the translational level. In addition, we also found that T2A inhibited the 
      angiogenesis and growth of human breast cancer xenografts in nude mice through 
      suppression of HIF-1alpha and VEGF. Our study provides novel perspectives and 
      potential targets for the treatment of human breast cancer.
FAU - Li, Guobing
AU  - Li G
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
FAU - Shan, Changyu
AU  - Shan C
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
FAU - Liu, Lei
AU  - Liu L
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
FAU - Zhou, Ting
AU  - Zhou T
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
FAU - Zhou, Jing
AU  - Zhou J
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
FAU - Hu, Xiaoye
AU  - Hu X
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
FAU - Chen, Yibiao
AU  - Chen Y
AD  - State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 
      China.
FAU - Cui, Hongjuan
AU  - Cui H
AD  - State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 
      China.
FAU - Gao, Ning
AU  - Gao N
AD  - College of Pharmacy, Third Military Medical University, Chongqing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150206
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Abietanes)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 03UUH3J385 (tanshinone)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Abietanes/*pharmacology
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Proteins/*metabolism
MH  - Neovascularization, Pathologic/*drug therapy/metabolism/pathology
MH  - Phosphoproteins/*metabolism
MH  - Ribosomal Protein S6/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Vascular Endothelial Growth Factor A/*biosynthesis
MH  - Xenograft Model Antitumor Assays
PMC - PMC4320086
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/02/07 06:00
MHDA- 2015/02/07 06:01
PMCR- 2015/02/06
CRDT- 2015/02/07 06:00
PHST- 2014/10/21 00:00 [received]
PHST- 2014/12/23 00:00 [accepted]
PHST- 2015/02/07 06:00 [entrez]
PHST- 2015/02/07 06:00 [pubmed]
PHST- 2015/02/07 06:01 [medline]
PHST- 2015/02/06 00:00 [pmc-release]
AID - PONE-D-14-47272 [pii]
AID - 10.1371/journal.pone.0117440 [doi]
PST - epublish
SO  - PLoS One. 2015 Feb 6;10(2):e0117440. doi: 10.1371/journal.pone.0117440. 
      eCollection 2015.