PMID- 18668345
OWN - NLM
STAT- MEDLINE
DCOM- 20090206
LR  - 20211203
IS  - 1423-0127 (Electronic)
IS  - 1021-7770 (Linking)
VI  - 15
IP  - 6
DP  - 2008 Nov
TI  - Arecoline and the 30-100 kDa fraction of areca nut extract differentially 
      regulate mTOR and respectively induce apoptosis and autophagy: a pilot study.
PG  - 823-31
LID - 10.1007/s11373-008-9273-8 [doi]
AB  - Areca nut (AN) is recognized as a human carcinogen; however, few studies of the 
      cytotoxic effects of AN ingredients on cells have been reported. In Taiwan, AN, 
      lime and inflorescence of Piper betle are the common components of betel quid 
      (BQ). We recently noticed that extract of AN (ANE), but not those of lime and 
      inflorescence of Piper betle, induces rounding cell morphology and nuclear 
      shrinkage in different types of carcinoma cells. In this study, the rounding cell 
      activity was first traced to the partially purified >or=10 kDa fraction (ANE >or= 
      10 K) and subsequently to the 30-100 kDa fraction (ANE 30-100 K). ANE and ANE 
      >or=10 K stimulated nuclear shrinkage (P < 0.001 in both cases) and the clearance 
      of the cytoplasm. ANE, ANE >or= 10 K, and ANE 30-100 K induced the cleavage of 
      LC3-I (P < 0.05, 0.01, and 0.05, respectively) and the emergence of autophagic 
      vacuoles (AVs) and acidic vesicles. On the other hand, arecoline (Are, the major 
      alkaloid of AN) triggered caspase-3 activation, peri-nuclear chromatin 
      condensation, and micronucleation. Meanwhile, ANE 30-100 K, but not Are, 
      inhibited the phosphorylation of the mammalian target of rapamycin 
      (mTOR)-Ser(2448). In conclusion, this study demonstrates that different AN 
      ingredients exerting differential impact on mTOR-Ser(2448) phosphorylation are 
      capable of triggering apoptosis and autophagy.
FAU - Liu, Shyun-Yeu
AU  - Liu SY
AD  - Oral and Maxillofacial Surgery Section, Chi Mei Medical Center, Tainan, Taiwan, 
      ROC.
FAU - Lin, Mei-Huei
AU  - Lin MH
FAU - Hsu, Yu-Rung
AU  - Hsu YR
FAU - Shih, Ya-Yun
AU  - Shih YY
FAU - Chiang, Wei-Fan
AU  - Chiang WF
FAU - Lee, Chin-Hai
AU  - Lee CH
FAU - Chou, Ta-Hsiung
AU  - Chou TH
FAU - Liu, Young-Chau
AU  - Liu YC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080731
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (Plant Extracts)
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 3.4.22.- (Caspase 3)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Areca/*chemistry
MH  - Autophagy/*drug effects
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Nuts
MH  - Phosphorylation/drug effects
MH  - Pilot Projects
MH  - Plant Extracts/*pharmacology
MH  - Protein Kinases/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Cells, Cultured
EDAT- 2008/08/01 09:00
MHDA- 2009/02/07 09:00
CRDT- 2008/08/01 09:00
PHST- 2008/04/17 00:00 [received]
PHST- 2008/07/17 00:00 [accepted]
PHST- 2008/08/01 09:00 [pubmed]
PHST- 2009/02/07 09:00 [medline]
PHST- 2008/08/01 09:00 [entrez]
AID - 10.1007/s11373-008-9273-8 [doi]
PST - ppublish
SO  - J Biomed Sci. 2008 Nov;15(6):823-31. doi: 10.1007/s11373-008-9273-8. Epub 2008 
      Jul 31.