[Up-regulation of NGF, trkA, Fas, down-regulation of bcl-2, and induction of apoptosis by propentofylline in human glioma cell lines].
Propentofylline (PPF) has been reported to stimulate the synthesis/secretion of nerve growth factor (NGF) by cultured mouse astroglial cells. In the present study, we examined whether PPF stimulates NGF synthesis in human glioma cell lines, the same as in mouse astroglial cells, and if so, whether NGF has a biological effect on glioma cells. After administration of PPF into the glioma cell lines, we investigated morphological changes and gene and protein expression of NGF, trkA, Fas and bcl-2 by using GFAP staining. Western blotting, and RT-PCR. Glioma cells showed definite morphological changes, including expansion of astrocytic processes, cytoplasmic enlargement and increases in GFAP staining. Interestingly, apoptosis was identified by DNA ladder formation in each of the cell lines. The mRNA and protein expression of NGF, trkA and Fas increased, but expression of bcl-2 decreased. These findings suggest that PPF works as a transcriptional modulator and induces apoptosis in glioma cells.
Kamada
H
H
Department of Neurosurgery, Hokuto Hospital, Japan.
Murakami
H
H
Satone
A
A
Ikeda
M
M
Yamaguchi
H
H
Matsumoto
A
A
Ide
W
W
Hashimoto
I
I
Ukita
H
H
D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D012194:RNA-Directed DNA Polymerase; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014970:Xanthines / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism*
D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014970:Xanthines; D019014:fas Receptor; C032114:propentofylline; D011505:Protein-Tyrosine Kinases; D012194:RNA-Directed DNA Polymerase