L-Leucine induces growth arrest and persistent ERK activation in glioma cells.
Glioma is the most common type of brain tumor, and has the worst prognosis in human malignancy. Experimental evidence suggests that the use of high concentrations of various amino acids may perturb neoplastic cell growth. Thus, the aim of this study was to investigate whether essential amino acids can alter the growth and proliferation of glioma cells. Studies were performed using C6 rat glioma cell lines. High concentration of L-leucine induced growth arrest of glioma cell lines. Terminal transferase uridyl nick end labeling assay and cell cycle analysis showed that the effect of L-leucine on glioma cells growth was not cytotoxic, but rather cytostatic. Additionally, the extracellular signal-regulated protein kinase was activated in L-leucine-treated glioma cells, and inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEK) enhanced the effect of L-leucine on glioma cell growth. These data suggest that high concentration L-leucine combined with inhibition of MEK is a potential strategy for glioma cell growth arrest.
Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. drne776@ndmc.ac.jp
Satoru
S
Takeuchi
Hiroshi
H
Nawashiro
Kojiro
K
Wada
Namiko
N
Nomura
Terushige
T
Toyooka
Naoki
N
Otani
Hideo
H
Osada
Hirotaka
H
Matsuo
Nariyoshi
N
Shinomiya
D000598:Amino Acids, Cyclic / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005910:Glioma; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000598:Amino Acids, Cyclic; D000970:Antineoplastic Agents; C530106:Ccnd1 protein, rat; D005419:Flavonoids; D027283:Large Neutral Amino Acid-Transporter 1; D019938:Cyclin D1; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007930:Leucine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one