PMID- 31228450
OWN - NLM
STAT- MEDLINE
DCOM- 20200121
LR  - 20211204
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 858
DP  - 2019 Sep 5
TI  - Anti-tumor efficacy of phellamurin in osteosarcoma cells: Involvement of the 
      PI3K/AKT/mTOR pathway.
PG  - 172477
LID - S0014-2999(19)30429-7 [pii]
LID - 10.1016/j.ejphar.2019.172477 [doi]
AB  - The extracts of Phellodendron amurense (P. amurense) have been shown to contain 
      many active ingredients e.g. flavone glycosides and to exert a wide range of 
      physiological activities including anti-tumor activity. However, the effects of 
      phellamurin (Phe), a plant flavonone glycoside from the leaves of P. amurense, on 
      osteosarcoma (OS) have never been reported. The effects of Phe on cell viability 
      and apoptosis were evaluated by MTT assay and flow cytometry analysis, 
      respectively. Western blot analysis was performed to detect the protein levels of 
      phosphorylated phosphatidylinositol 3 kinase (PI3K) (p-PI3K), phosphorylated 
      protein kinase B (AKT) (p-AKT), AKT, phosphorylated mammalian target of rapamycin 
      (mTOR) (p-mTOR), and mTOR. We found that Phe suppressed the viability and 
      promoted apoptosis in OS cells in a dose-dependent manner. Notably, Phe repressed 
      the PI3K/AKT/mTOR pathway in OS cells. LY294002 effectively inhibited the 
      PI3K/AKT/mTOR signaling pathway, repressed cell viability and induced apoptosis 
      in OS cells. Activation of PI3K/AKT/mTOR pathway by 740Y-P abolished the effects 
      of Phe on the viability and apoptosis of OS cells. We also found that Phe 
      repressed OS tumor growth and inhibited the PI3K/AKT/mTOR pathway in vivo. In 
      conclusion, Phe suppressed the viability and induced apoptosis in OS cells, at 
      least, partially by inhibiting the PI3K/AKT/mTOR pathway. Our study suggested 
      that Phe might be a new and potential chemotherapeutic agent for the treatment of 
      OS.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Zhang, Hongzhi
AU  - Zhang H
AD  - Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, 475000, 
      PR China. Electronic address: zhz_7607@126.com.
FAU - Jiang, Huijuan
AU  - Jiang H
AD  - Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, 475000, 
      PR China.
FAU - Zhang, Huixiang
AU  - Zhang H
AD  - Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, 475000, 
      PR China.
FAU - Liu, Juncai
AU  - Liu J
AD  - Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, 475000, 
      PR China.
FAU - Hu, Xigang
AU  - Hu X
AD  - Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, 475000, 
      PR China.
FAU - Chen, Lei
AU  - Chen L
AD  - Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, 475000, 
      PR China.
LA  - eng
PT  - Journal Article
DEP - 20190620
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Flavonoids)
RN  - 52589-11-4 (phellamurin)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Female
MH  - Flavonoids/*pharmacology
MH  - Humans
MH  - Mice
MH  - Osteosarcoma/*pathology
MH  - Phosphatidylinositol 3-Kinase/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Apoptosis
OT  - Osteosarcoma
OT  - PI3K/AKT/mTOR pathway
OT  - Phellamurin
OT  - Viability
EDAT- 2019/06/23 06:00
MHDA- 2020/01/22 06:00
CRDT- 2019/06/23 06:00
PHST- 2019/03/06 00:00 [received]
PHST- 2019/06/17 00:00 [revised]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/06/23 06:00 [pubmed]
PHST- 2020/01/22 06:00 [medline]
PHST- 2019/06/23 06:00 [entrez]
AID - S0014-2999(19)30429-7 [pii]
AID - 10.1016/j.ejphar.2019.172477 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Sep 5;858:172477. doi: 10.1016/j.ejphar.2019.172477. Epub 
      2019 Jun 20.