PMID- 24889814
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20161125
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 45
IP  - 2
DP  - 2014 Aug
TI  - The novel pterostilbene derivative ANK-199 induces autophagic cell death through 
      regulating PI3 kinase class III/beclin 1/Atg‑related proteins in 
      cisplatin‑resistant CAR human oral cancer cells.
PG  - 782-94
LID - 10.3892/ijo.2014.2478 [doi]
AB  - Pterostilbene is an effective chemopreventive agent against multiple types of 
      cancer cells. A novel pterostilbene derivative, ANK-199, was designed and 
      synthesized by our group. Its antitumor activity and mechanism in 
      cisplatin-resistant CAR human oral cancer cells were investigated in this study. 
      Our results show that ANK-199 has an extremely low toxicity in normal oral cell 
      lines. The formation of autophagic vacuoles and acidic vesicular organelles 
      (AVOs) was observed in the ANK-199-treated CAR cells by monodansylcadaverine 
      (MDC) and acridine orange (AO) staining, suggesting that ANK-199 is able to 
      induce autophagic cell death in CAR cells. Neither DNA fragmentation nor DNA 
      condensation was observed, which means that ANK-199-induced cell death is not 
      triggered by apoptosis. In accordance with morphological observation, 3-MA, a 
      specific inhibitor of PI3K kinase class III, can inhibit the autophagic vesicle 
      formation induced by ANK-199. In addition, ANK-199 is also able to enhance the 
      protein levels of autophagic proteins, Atg complex, beclin 1, PI3K class III and 
      LC3-II, and mRNA expression of autophagic genes Atg7, Atg12, beclin 1 and LC3-II 
      in the ANK-199-treated CAR cells. A molecular signaling pathway induced by 
      ANK-199 was therefore summarized. Results presented in this study show that 
      ANK-199 may become a novel therapeutic reagent for the treatment of oral cancer 
      in the near future (patent pending).
FAU - Hsieh, Min-Tsang
AU  - Hsieh MT
AD  - School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C.
FAU - Chen, Hao-Ping
AU  - Chen HP
AD  - Department of Biochemistry, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
FAU - Lu, Chi-Cheng
AU  - Lu CC
AD  - Department of Food Science and Biotechnology, National Chung Hsing University, 
      Taichung 402, Taiwan, R.O.C.
FAU - Chiang, Jo-Hua
AU  - Chiang JH
AD  - Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, 
      R.O.C.
FAU - Wu, Tian-Shung
AU  - Wu TS
AD  - Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, 
      R.O.C.
FAU - Kuo, Daih-Huang
AU  - Kuo DH
AD  - Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen 
      University, Pingtung 907, Taiwan, R.O.C.
FAU - Huang, Li-Jiau
AU  - Huang LJ
AD  - Graduate Institute of Pharmaceutical Chemistry, China Medical University, 
      Taichung 404, Taiwan, R.O.C.
FAU - Kuo, Sheng-Chu
AU  - Kuo SC
AD  - Graduate Institute of Pharmaceutical Chemistry, China Medical University, 
      Taichung 404, Taiwan, R.O.C.
FAU - Yang, Jai-Sing
AU  - Yang JS
AD  - Department of Pharmacology, China Medical University, Taichung 404, Taiwan, 
      R.O.C.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140602
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (ANK-199)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Membrane Proteins)
RN  - 0 (Stilbenes)
RN  - 26R60S6A5I (pterostilbene)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/*drug effects
MH  - Beclin-1
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cisplatin/pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Mouth Neoplasms/*metabolism/pathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Polymerase Chain Reaction
MH  - Stilbenes/*pharmacokinetics/*pharmacology
EDAT- 2014/06/04 06:00
MHDA- 2015/01/27 06:00
CRDT- 2014/06/04 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2014/05/02 00:00 [accepted]
PHST- 2014/06/04 06:00 [entrez]
PHST- 2014/06/04 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
AID - 10.3892/ijo.2014.2478 [doi]
PST - ppublish
SO  - Int J Oncol. 2014 Aug;45(2):782-94. doi: 10.3892/ijo.2014.2478. Epub 2014 Jun 2.