PMID- 19811732
OWN - NLM
STAT- MEDLINE
DCOM- 20100315
LR  - 20091008
IS  - 1007-8738 (Print)
IS  - 1007-8738 (Linking)
VI  - 25
IP  - 10
DP  - 2009 Oct
TI  - [Cell proliferation inhibited by TIP-6 through autophagy in human hepatoma cell 
      line HepG2 and human normal hepatocyte cell line L02].
PG  - 883-6
AB  - AIM: To investigate the effect of 7-(4-methoxyphenyl)-5, 8a-diphenyl-1, 2, 3, 7, 
      8, 8a-hexahydroimidazo[1, 2-a]pyridine (TIP-6) on cell proliferation in human 
      hepatoma cell line HepG2 and human normal hepatocyte cell line L02. METHODS: 
      Typan blue assay was used to check the effect of TIP-6 on cell proliferation. The 
      changes of cell morphology were observed by the phase contrast microscope. Flow 
      cytometry (FCM) was used to check cell cycle. Autophagy and autophagic cell death 
      were detected after acridine orange (AO) staining under fluorescent microscopy. 
      Apoptosis was analyzed by Annexin V/7-AAD, DAPI staining and DNA ladder. 
      NF-kappaB expression was detected with cellular immunochemistry. RESULTS: Cell 
      proliferation inhibiting effect was appeared when treated with TIP-6 from 60 
      mumol/L to 200 mumol/L, which was correlated with treated concentrations and 
      time. The proliferation rates were just 12.10% and 18.75% (vs control) under 200 
      mumol/L 72 h in HepG2 and L02 respectively. Vacuolization were found more and 
      more frequently with the increasing of TIP-6 concentrations and treated time 
      prolonged. FCM results indicated that cells were blocked in G2/M phase, and more 
      sensitive were found in HepG2 than L02. AO staining results indicated that the 
      phenomenon of autophagy and autophagic cell death were occurred and appeared more 
      potent with more TIP-6 and longer time treated. No apoptosis markers were found 
      with Annexin V/7-AAD and DAPI staining, and no DNA ladders were found either, 
      these indicated that TIP-6 didn't induce apoptosis in these cells. NF-kappaB was 
      found increased after treated with TIP-6, and the autophagic vacuole became more 
      and more with the increasing of NF-kappaB protein, but the proliferation rates 
      decreased at the same time. CONCLUSION: TIP-6 inhibited cell proliferation and 
      induced autophagy and autophagic cell death in HepG2 and L02 cells. NF-kappaB 
      activation may be involved in these effects.
FAU - Gao, Xiao-Fei
AU  - Gao XF
AD  - School of Life Sciences, Lanzhou University, Lanzhou 730000, China. 
      gxfei427@126.com
FAU - Hai, Jun
AU  - Hai J
FAU - Du, Yu-Ping
AU  - Du YP
FAU - Wang, Qin
AU  - Wang Q
FAU - Hui, Xin-Ping
AU  - Hui XP
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
JT  - Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular 
      immunology
JID - 101139110
RN  - 0 (7-(4-methoxyphenyl)-5,8a-diphenyl-1,2,3,7, 
      8,8a-hexahydroimidazo(1,2-a)pyridine)
RN  - 0 (Pyridines)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Carcinoma, Hepatocellular/*pathology
MH  - Cell Count
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Hepatocytes/*cytology/drug effects
MH  - Humans
MH  - Pyridines/*pharmacology
MH  - Time Factors
EDAT- 2009/10/09 06:00
MHDA- 2010/03/17 06:00
CRDT- 2009/10/09 06:00
PHST- 2009/10/09 06:00 [entrez]
PHST- 2009/10/09 06:00 [pubmed]
PHST- 2010/03/17 06:00 [medline]
PST - ppublish
SO  - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Oct;25(10):883-6.