PMID- 27056897
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20211204
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 19
DP  - 2016 May 10
TI  - Icariside II, a natural mTOR inhibitor, disrupts aberrant energy homeostasis via 
      suppressing mTORC1-4E-BP1 axis in sarcoma cells.
PG  - 27819-37
LID - 10.18632/oncotarget.8538 [doi]
AB  - The aberrant energy homeostasis that characterized by high rate of energy 
      production (glycolysis) and energy consumption (mRNA translation) is associated 
      with the development of cancer. As mammalian target of rapamycin (mTOR) is a 
      critical regulator of aberrant energy homeostasis, it is an attractive target for 
      anti-tumor intervention. The flavonoid compound Icariside II (IS) is a natural 
      mTOR inhibitor derived from Epimedium. Koreanum. Herein, we evaluate the effect 
      of IS on aberrant energy homeostasis. The reduction of glycolysis and mRNA 
      translation in U2OS (osteosarcoma), S180 (fibrosarcoma) and SW1535 
      (chondrosarcoma) cells observed in our study, indicate that, IS inhibits aberrant 
      energy homeostasis. This inhibition is found to be due to suppression of 
      mammalian target of rapamycin complex 1 (mTORC1)-eukaryotic translation 
      initiation factor 4E-binding protein 1 (4E-BP1) axis through blocking the 
      assembly of mTORC1. Furthermore, IS inhibits the cap-dependent translation of 
      c-myc through mTORC1-4E-BP1 axis which links the relationship between mRNA 
      translation and glycolysis. Inhibition of aberrant energy homeostasis by IS, 
      contributes to its in vitro and in vivo anti-proliferation activity. These data 
      indicate that IS disrupts aberrant energy homeostasis of sarcoma cells through 
      suppression of mTORC1-4E-BP1 axis, providing a novel mechanism of IS to inhibit 
      cell proliferation in sarcoma cells.
FAU - Zhang, Chao
AU  - Zhang C
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Yang, Lei
AU  - Yang L
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Geng, Ya-di
AU  - Geng YD
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - An, Fa-Liang
AU  - An FL
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Xia, Yuan-Zheng
AU  - Xia YZ
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Guo, Chao
AU  - Guo C
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Luo, Jian-Guang
AU  - Luo JG
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Zhang, Lu-Yong
AU  - Zhang LY
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Guo, Qing-Long
AU  - Guo QL
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
FAU - Kong, Ling-Yi
AU  - Kong LY
AD  - State Key Laboratory of Natural Medicines, Department of Natural Medicinal 
      Chemistry, China Pharmaceutical University, Nanjing, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Flavonoids)
RN  - 0 (MYC protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RICTOR protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RPTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 113558-15-9 (baohuoside I)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Drugs, Chinese Herbal/*pharmacology/therapeutic use
MH  - Epimedium/*chemistry
MH  - Flavonoids/*pharmacology/therapeutic use
MH  - Glycolysis/drug effects
MH  - Homeostasis/*drug effects
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Phosphoproteins/genetics/*metabolism
MH  - Protein Biosynthesis/drug effects
MH  - Proto-Oncogene Proteins c-myc/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Rapamycin-Insensitive Companion of mTOR Protein/genetics
MH  - Regulatory-Associated Protein of mTOR/genetics
MH  - Sarcoma/*drug therapy
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC5053690
OTO - NOTNLM
OT  - Icariside II
OT  - aberrant energy homeostasis
OT  - glycolysis
OT  - mRNA translation
OT  - mTORC1-4E-BP1 axis
COIS- The authors declare no competing financial interests.
EDAT- 2016/04/09 06:00
MHDA- 2017/12/12 06:00
PMCR- 2016/05/10
CRDT- 2016/04/09 06:00
PHST- 2015/07/20 00:00 [received]
PHST- 2016/03/23 00:00 [accepted]
PHST- 2016/04/09 06:00 [entrez]
PHST- 2016/04/09 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2016/05/10 00:00 [pmc-release]
AID - 8538 [pii]
AID - 10.18632/oncotarget.8538 [doi]
PST - ppublish
SO  - Oncotarget. 2016 May 10;7(19):27819-37. doi: 10.18632/oncotarget.8538.