PMID- 20959361
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20211203
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Linking)
VI  - 79
IP  - 1
DP  - 2011 Jan
TI  - Curcumin dually inhibits both mammalian target of rapamycin and nuclear factor-kappaB 
      pathways through a crossed phosphatidylinositol 3-kinase/Akt/IkappaB kinase complex 
      signaling axis in adenoid cystic carcinoma.
PG  - 106-18
LID - 10.1124/mol.110.066910 [doi]
AB  - Adenoid cystic carcinoma (ACC) is a highly malignant tumor that is generally 
      unresponsive or only weakly responsive to the currently available antineoplastic 
      agents. Thus, novel therapeutic strategies and agents are urgently needed to 
      treat this aggressive neoplasm. Curcumin, a component of turmeric (Curcuma 
      longa), has been shown to have a diversity of antitumor activities. We show here 
      that curcumin is a potent inhibitor of ACC progression in vitro and in vivo. 
      Curcumin concentration-dependently inhibited the growth of ACC cells via 
      induction of apoptosis. The ability of ACC cells to migrate/invade and induce 
      angiogenesis was also significantly attenuated by curcumin, accompanied by the 
      down-regulation of vascular endothelial growth factor (VEGF) and matrix 
      metalloproteinase-2 and -9. Moreover, our data also demonstrated that the 
      inhibitory effects of curcumin on ACC cells were due to its dual inhibition of 
      both mammalian target of rapamycin (mTOR) and nuclear factor-kappaB (NF-kappaB) pathways 
      through a crossed phosphatidylinositol 3-kinase/Akt/IkappaBalpha kinase signaling axis. 
      Most importantly, curcumin effectively prevented the in vivo growth and 
      angiogenesis of ACC xenografts in nude mice, as revealed by the induction of cell 
      apoptosis and reduction of microvessel density in tumor tissues. In addition, we 
      further assessed the nature activation status of both mTOR and NF-kappaB pathways in 
      ACC tissues and confirmed the concurrent high activation of these two pathways in 
      ACC for the first time. Taken together, our findings suggest that further 
      clinical investigation is warranted to apply curcumin as a novel chemotherapeutic 
      regimen for ACC because of its dual suppression of both mTOR and NF-kappaB pathways.
FAU - Sun, Zhi-Jun
AU  - Sun ZJ
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key 
      Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, 
      China.
FAU - Chen, Gang
AU  - Chen G
FAU - Zhang, Wei
AU  - Zhang W
FAU - Hu, Xiang
AU  - Hu X
FAU - Liu, Yang
AU  - Liu Y
FAU - Zhou, Qian
AU  - Zhou Q
FAU - Zhu, Ling-Xing
AU  - Zhu LX
FAU - Zhao, Yi-Fang
AU  - Zhao YF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101019
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (I kappa B beta protein)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
EIN - Mol Pharmacol. 2011 Mar;79(3):628-30
MH  - Animals
MH  - Carcinoma, Adenoid Cystic/drug therapy/*enzymology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Chickens
MH  - Curcumin/*pharmacology/therapeutic use
MH  - Female
MH  - I-kappa B Proteins/*antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Random Allocation
MH  - Rats
MH  - Signal Transduction/*drug effects/physiology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Xenograft Model Antitumor Assays/methods
EDAT- 2010/10/21 06:00
MHDA- 2011/01/14 06:00
CRDT- 2010/10/21 06:00
PHST- 2010/10/21 06:00 [entrez]
PHST- 2010/10/21 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
AID - mol.110.066910 [pii]
AID - 10.1124/mol.110.066910 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2011 Jan;79(1):106-18. doi: 10.1124/mol.110.066910. Epub 2010 Oct 
      19.