PMID- 19723512
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20220316
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 79
IP  - 2
DP  - 2010 Jan 15
TI  - Antroquinonol displays anticancer potential against human hepatocellular 
      carcinoma cells: a crucial role of AMPK and mTOR pathways.
PG  - 162-71
LID - 10.1016/j.bcp.2009.08.022 [doi]
AB  - 5'AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin 
      (mTOR) are two serine/threonine protein kinases responsible for cellular energy 
      homeostasis and translational control, respectively. Evidence suggests that these 
      two kniases are potential targets for cancer chemotherapy against hepatocellular 
      carcinoma (HCC). Antroquinonol that is isolated from Antrodia camphorate, a 
      well-known Traditional Chinese Medicine for treatment of liver diseases, 
      displayed effective anticancer activity against both HBV DNA-positive and 
      -negative HCC cell lines. The rank order of potency against HCCs is 
      HepG2>HepG2.2.15>Mahlavu>PLC/PRF/5>SK-Hep1>Hep3B. Antroquinonol completely 
      abolished cell-cycle progression released from double-thymidine-block 
      synchronization and caused a subsequent apoptosis. The data were supported by 
      down-regulation and reduced nuclear translocation of G1-regulator proteins, 
      including cyclin D1, cyclin E, Cdk4 and Cdk2. Further analysis showed that the 
      mRNA expressions of the G1-regulator proteins were not modified by antroquinonol, 
      indicating an inhibition of translational but not transcriptional levels. 
      Antroquinonol induced the assembly of tuberous sclerosis complex (TSC)-1/TSC2, 
      leading to the blockade of cellular protein synthesis through inhibition of 
      protein phosphorylation including mTOR (Ser(2448)), p70(S6K) (Thr(421)/Ser(424) 
      and Thr(389)) and 4E-BP1 (Thr(37)/Thr(46) and Thr(70)). Furthermore, the AMPK 
      activity was elevated by antroquinonol. Compound C, a selective AMPK inhibitor, 
      significantly reversed antroquinonol-mediated effects suggesting the crucial role 
      of AMPK. Besides, the loss of mitochondrial membrane potential and depletion of 
      mitochondrial content indicated the mitochondrial stress caused by antroquinonol. 
      In summary, the data suggest that antroquinonol displays anticancer activity 
      against HCCs through AMPK activation and inhibition of mTOR translational 
      pathway, leading to G1 arrest of the cell-cycle and subsequent cell apoptosis.
FAU - Chiang, Po-Cheng
AU  - Chiang PC
AD  - School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Rd, Taipei 
      100, Taiwan.
FAU - Lin, Ssu-Chia
AU  - Lin SC
FAU - Pan, Shiow-Lin
AU  - Pan SL
FAU - Kuo, Ching-Hua
AU  - Kuo CH
FAU - Tsai, I-Lin
AU  - Tsai IL
FAU - Kuo, Mao-Tien
AU  - Kuo MT
FAU - Wen, Wu-Che
AU  - Wen WC
FAU - Chen, Peini
AU  - Chen P
FAU - Guh, Jih-Hwa
AU  - Guh JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090831
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (DNA Primers)
RN  - 1339-63-5 (Ubiquinone)
RN  - AX9P92T7JZ (antroquinonol)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.4.3 (Adenylate Kinase)
SB  - IM
MH  - Adenylate Kinase/*metabolism
MH  - Base Sequence
MH  - Carcinoma, Hepatocellular/*pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - DNA Primers
MH  - Flow Cytometry
MH  - Humans
MH  - Liver Neoplasms/*pathology
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases
MH  - Ubiquinone/*analogs & derivatives/pharmacology
EDAT- 2009/09/03 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/09/03 09:00
PHST- 2009/06/27 00:00 [received]
PHST- 2009/08/21 00:00 [revised]
PHST- 2009/08/24 00:00 [accepted]
PHST- 2009/09/03 09:00 [entrez]
PHST- 2009/09/03 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S0006-2952(09)00702-3 [pii]
AID - 10.1016/j.bcp.2009.08.022 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2010 Jan 15;79(2):162-71. doi: 10.1016/j.bcp.2009.08.022. Epub 
      2009 Aug 31.