PMID- 23178381
OWN - NLM
STAT- MEDLINE
DCOM- 20130422
LR  - 20191210
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 201
IP  - 1-3
DP  - 2013 Jan 25
TI  - Aspidin PB, a phloroglucinol derivative, induces apoptosis in human 
      hepatocarcinoma HepG2 cells by modulating PI3K/Akt/GSK3beta pathway.
PG  - 1-8
LID - S0009-2797(12)00240-2 [pii]
LID - 10.1016/j.cbi.2012.11.005 [doi]
AB  - Aspidin PB, a phloroglucinol derivative isolated from Dryopteris fragrans (L.) 
      Schott, has been previously reported to exert high biological activities. In the 
      present study, we analyzed the apoptotic mechanisms of aspidin PB on human 
      hepatoma cell line, HepG2. Initially, aspidin PB was shown to inhibit the growth 
      of HepG2 cells in a time and dose-dependent manner. After treatment with aspidin 
      PB for 72 h, 48 h and 24 h using MTT assay, the IC(50) values were 10.59 muM, 
      20.86 muM and 46.59 muM, respectively. Aspidin PB was capable to induce apoptosis, 
      as measured by mitochondrial membrane potential (DeltaPsim), acridine orange (AO) 
      staining and propidium iodide (PI)/annexin V-FITC double staining. To further 
      explore the signaling pathway of aspidin PB-mediated apoptosis, we examined 
      PI3K/Akt related proteins. Western blot analysis revealed that aspidin PB 
      inhibited PI3K expression, phosphorylation of Ser473 Akt and Ser9 GSK3beta followed 
      by up-regulation of nonsteroidal anti-inflammatory drugs activated gene-1 (NAG-1) 
      expression. Similarly, the effects of aspidin PB on PI3K, Akt, GSK3beta, NAG-1 
      expression were abolished by treatment with the PI3K inhibitor, wortmannin. Taken 
      together, our data suggested that the PI3K/Akt/GSK3beta signal pathway may represent 
      one of the major mechanisms of the effects of aspidin PB on human hepatocarcinoma 
      cells.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Sun, Yao
AU  - Sun Y
AD  - Engineering Research Center of Forest Bio-Preparation, Ministry of Education, 
      Northeast Forestry University, Harbin 150040, PR China.
FAU - Gao, Chang
AU  - Gao C
FAU - Luo, Meng
AU  - Luo M
FAU - Wang, Wei
AU  - Wang W
FAU - Gu, Chengbo
AU  - Gu C
FAU - Zu, Yuangang
AU  - Zu Y
FAU - Li, Ji
AU  - Li J
FAU - Efferth, Thomas
AU  - Efferth T
FAU - Fu, Yujie
AU  - Fu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121121
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Androstadienes)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - DHD7FFG6YS (Phloroglucinol)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Apoptosis/*drug effects
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Cell Proliferation/drug effects
MH  - Flow Cytometry
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/metabolism/pathology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Microscopy, Confocal
MH  - Phloroglucinol/*analogs & derivatives/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - Wortmannin
EDAT- 2012/11/28 06:00
MHDA- 2013/04/23 06:00
CRDT- 2012/11/27 06:00
PHST- 2012/07/21 00:00 [received]
PHST- 2012/10/15 00:00 [revised]
PHST- 2012/11/06 00:00 [accepted]
PHST- 2012/11/27 06:00 [entrez]
PHST- 2012/11/28 06:00 [pubmed]
PHST- 2013/04/23 06:00 [medline]
AID - S0009-2797(12)00240-2 [pii]
AID - 10.1016/j.cbi.2012.11.005 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2013 Jan 25;201(1-3):1-8. doi: 10.1016/j.cbi.2012.11.005. 
      Epub 2012 Nov 21.