PMID- 27997894
OWN - NLM
STAT- MEDLINE
DCOM- 20170208
LR  - 20211204
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 40
IP  - 6
DP  - 2016
TI  - Zedoarondiol Inhibits Platelet-Derived Growth Factor-Induced Vascular Smooth 
      Muscle Cells Proliferation via Regulating AMP-Activated Protein Kinase Signaling 
      Pathway.
PG  - 1506-1520
LID - 10.1159/000453201 [doi]
AB  - BACKGROUND/AIMS: Vascular smooth muscle cells (VSMCs) proliferation contributes 
      significantly to atherosclerosis and in-stent restenosis. Platelet-derived growth 
      factor-BB (PDGF-BB) plays a vital role in VSMCs proliferation. Zedoarondiol, a 
      sesquiterpene lactone compound, has an anti-inflammatory activity. However, the 
      role of zedoarondiol in PDGF-BB-mediated VSMCs proliferation remains unclear. In 
      this study, we investigated the effects of zedoarondiol on PDGF-BB-induced VSMCs 
      proliferation and explored the possible mechanisms. METHODS: The inhibitory 
      effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation were evaluated by 
      direct cell counting and the Cell Counting Kit-8 (CCK-8) assay. DNA synthesis was 
      examined by bromodeoxyuridine (BrdU) incorporation assay. Cell cycle was assessed 
      by propidium iodide staining. Western blotting was performed to determine the 
      expression of cyclin-dependent kinase 2 (CDK2), cyclin E, p53, p21, total and 
      phosphorylated adenosine monophosphate-activated protein kinase (AMPK), acetyl 
      CoA carboxylase (ACC), mammalian target of rapamycin (mTOR), and p70 ribosomal 
      protein S6 kinase (p70S6K). RESULTS: Zedoarondiol suppressed PDGF-BB-induced 
      VSMCs proliferation and DNA synthesis, and induced cell cycle arrest in G0/G1 
      phase. In addition, zedoarondiol activated AMPK and ACC, inhibited the 
      phosphorylation of mTOR and p70S6K, increased the expression of p53 and p21, and 
      decreased the expression of CDK2 and cyclin E. Compound C (an AMPK inhibitor) 
      abrogated, whereas 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR, an 
      AMPK activator) enhanced zedoarondiol-mediated inhibition of VSMCs proliferation 
      and DNA synthesis. CONCLUSION: Zedoarondiol inhibits PDGF-BB-induced VSMCs 
      proliferation via AMPK-mediated down-regulation of the mTOR/p70S6K pathway and 
      up-regulation of the p53/p21 pathway. These findings suggest that zedoarondiol 
      might be a promising compound against atherosclerosis and in-stent restenosis.
CI  - (c) 2016 The Author(s) Published by S. Karger AG, Basel.
FAU - Mao, Huimin
AU  - Mao H
AD  - Graduate School, Beijing University of Chinese Medicine, Beijing, China.
FAU - Tao, Tianqi
AU  - Tao T
FAU - Song, Dandan
AU  - Song D
FAU - Liu, Mi
AU  - Liu M
FAU - Wang, Xiaoren
AU  - Wang X
FAU - Liu, Xiuhua
AU  - Liu X
FAU - Shi, Dazhuo
AU  - Shi D
LA  - eng
PT  - Journal Article
DEP - 20161221
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Lactones)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (zedoarondiol)
RN  - 1B56C968OA (Becaplermin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Becaplermin
MH  - Cell Cycle Checkpoints
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cyclin-Dependent Kinase 2/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - DNA/biosynthesis
MH  - Down-Regulation/drug effects
MH  - Enzyme Activation/drug effects
MH  - G1 Phase/drug effects
MH  - Humans
MH  - Lactones/chemistry/*pharmacology
MH  - Male
MH  - Models, Biological
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Myocytes, Smooth Muscle/*cytology/drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-sis/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Resting Phase, Cell Cycle/drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Sesquiterpenes/chemistry/*pharmacology
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2016/12/21 06:00
MHDA- 2017/02/09 06:00
CRDT- 2016/12/21 06:00
PHST- 2016/11/09 00:00 [accepted]
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
PHST- 2016/12/21 06:00 [entrez]
AID - 000453201 [pii]
AID - 10.1159/000453201 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2016;40(6):1506-1520. doi: 10.1159/000453201. Epub 2016 Dec 
      21.