PMID- 24162829
OWN - NLM
STAT- MEDLINE
DCOM- 20140902
LR  - 20211021
IS  - 1573-7373 (Electronic)
IS  - 0167-594X (Linking)
VI  - 116
IP  - 2
DP  - 2014 Jan
TI  - 18beta-glycyrrhetinic acid induces apoptosis in pituitary adenoma cells via 
      ROS/MAPKs-mediated pathway.
PG  - 221-30
LID - 10.1007/s11060-013-1292-2 [doi]
AB  - The purpose of the present study was to evaluate the anti-tumor effects of 
      18beta-glycyrrhetinic acid (GA), a natural compound extracted from liquorice, 
      against pituitary adenoma and its underlying mechanisms in cultured cells and 
      mouse model of xenografted tumor. GA induced cellular damage in rat pituitary 
      adenoma-derived MMQ and GH3 cells, manifested as reduced cell viability, 
      increased lactate dehydrogenase release, elevated intracellular reactive oxygen 
      species (ROS) and Ca(2+) concentration. GA also caused G0/G1 phase arrest, 
      increased apoptosis rate and increased mitochondrial membrane permeabilization by 
      suppressing the mitochondrial membrane potential and down-regulating a ratio of B 
      cell lymphoma 2 (Bcl-2) and Bax. GA activated calcium/calmodulin-dependent 
      protein kinase II (CaMKII), c-Jun N-terminal kinase (JNK) and P38; but these 
      activating effects were attenuated by pretreatment with N-acetyl-L-cysteine, a 
      ROS inhibitor. Pretreatment with KN93, a CaMKII inhibitor, also abolished the GA 
      activation of JNK and P38. GA remarkably inhibited growth of pituitary adenoma 
      grafted on nude mice. These results suggest that the anti-pituitary adenoma 
      effect of GA is associated with its apoptotic actions by activating 
      mitochondria-mediated ROS/mitogen-activated protein kinase pathways in particular 
      CaMKII that may serve a linkage between ROS accumulation and the activation of 
      JNK and P38. This study provides experimental evidence in the support of further 
      developing GA as a chemotherapeutic agent for pituitary adenoma.
FAU - Wang, Di
AU  - Wang D
AD  - School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
FAU - Wong, Hei-Kiu
AU  - Wong HK
FAU - Feng, Yi-Bin
AU  - Feng YB
FAU - Zhang, Zhang-Jin
AU  - Zhang ZJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131027
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 1449-05-4 (18alpha-glycyrrhetinic acid)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - P540XA09DR (Glycyrrhetinic Acid)
SB  - IM
MH  - Adenoma/drug therapy/*pathology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Glycyrrhetinic Acid/*analogs & derivatives/pharmacology/therapeutic use
MH  - Humans
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Mice, Nude
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Pituitary Neoplasms/drug therapy/*pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - Time Factors
MH  - Transplantation, Heterologous/methods
EDAT- 2013/10/29 06:00
MHDA- 2014/09/03 06:00
CRDT- 2013/10/29 06:00
PHST- 2013/05/15 00:00 [received]
PHST- 2013/10/21 00:00 [accepted]
PHST- 2013/10/29 06:00 [entrez]
PHST- 2013/10/29 06:00 [pubmed]
PHST- 2014/09/03 06:00 [medline]
AID - 10.1007/s11060-013-1292-2 [doi]
PST - ppublish
SO  - J Neurooncol. 2014 Jan;116(2):221-30. doi: 10.1007/s11060-013-1292-2. Epub 2013 
      Oct 27.