5-lipoxygenase pathway promotes cell proliferation in human glioma cell lines.
OBJECTIVE
5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes (LTs), that might promote carcinogenesis. We investigated 5-LO expression and examined whether the 5-LO pathway is associated with the proliferation of human brain tumors.


METHODS
We immunohistochemically evaluated the profile of 5-LO expression in various types of brain tumors obtained from 42 patients, and examined the proliferative effects of the 5-LO pathway in human glioma cell lines using a proliferation assay.


RESULTS
Immunohistochemistry of glioblastomas, astrocytomas, meningiomas, medulloblastomas, craniopharyngiomas, ependymomas, neurinomas, oligodendrogliomas, malignant lymphomas, dysembryoplastic neuroepithelial and metastatic brain tumors revealed 5-LO expression in the cytoplasm and nuclei or nuclear envelopes of tumor cells. The 5-LO inhibitor A861 and the LTA4 hydrolase inhibitor Bestatin dose-dependently suppressed the proliferation of A172 cells, a glioma cell line.


CONCLUSIONS
We confirmed the expression of 5-LO in various human brain tumors and demonstrated the partial suppression of tumor growth by inhibitors of the 5-LO-LTA4 hydrolase pathway in human glioma cell lines. The 5-LO-LTA4 pathway might play roles in the proliferation of human glioma cells.
Ishii
K
K
Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Nagasaki, Japan.
Zaitsu
M
M
Yonemitsu
N
N
Kan
Y
Y
Hamasaki
Y
Y
Matsuo
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D001254:Astrocytoma / Q000473:pathology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000503:physiopathology; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D017572:Leukotriene A4 / Q000037:antagonists & inhibitors / Q000502:physiology; D016859:Lipoxygenase Inhibitors; D008297:Male; D008579:Meningioma / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured; D055815:Young Adult
D017572:Leukotriene A4; D016859:Lipoxygenase Inhibitors; D011480:Protease Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D007930:Leucine; C012211:ubenimex