Inhibitory effects of sodium butyrate on proliferation and invasiveness of human glioma cells.
OBJECTIVE
Sodium butyrate (SB), a differentiation-inducing agent, has been demonstrated to inhibit cellular proliferation in a number of human cell lines. Its precise mechanisms remain to be clarified, however. We investigated molecular mechanisms of SB-induced growth suppression as well as the effects of SB on the invasiveness of human glioma cells.


METHODS
Human glioma U87MG and U251MG cells were treated with 1 or 2 mmol/L SB for 48 hours, and the inhibition of cell growth was assessed by spectrophotometric analysis. Cell cycle analysis was carried out by the 5-bromo-2'-deoxyuridine incorporation method, and expression of cell cycle-regulatory proteins was determined by immunoblotting. In addition, invasiveness was assessed using a Transwell chamber (Iwaki, Tokyo, Japan) with extracellular matrix substrate fibronectin or laminin (Iwaki).


RESULTS
SB treatment resulted in significantly suppressed proliferation of both U87MG and U251MG cells in a dose-dependent manner. It inhibited the G1-S transition, which was associated with increased expression of p21 and cyclin D1 and reduced pRb phosphorylation. Treatment with antisense oligonucleotide for Rb abrogated SB-induced G1 arrest. p21 up-regulation was independent of the p53 status of the glioma cells. SB treatment also inhibited invasiveness on fibronectin and laminin.


CONCLUSIONS
Our results indicate that SB may suppress the growth of human glioma cells through modulation of cell cycle progression and also may affect their invasiveness on extracellular matrix substrates, which suggests that SB may be a useful therapeutic agent in treating multiple aspects of malignant gliomas.
Ito
N
N
Department of Neurosurgery, Akiru Municipal General Hospital, Akiruno, Tokyo, Japan. nito-kyr@umin.ac.jp
Sawa
H
H
Nagane
M
M
Noguchi
A
A
Hara
M
M
Saito
I
I
D001932:Brain Neoplasms / Q000473:pathology*; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016193:G1 Phase; D005910:Glioma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D016196:S Phase; D014407:Tumor Cells, Cultured
D002087:Butyrates; D018797:Cell Cycle Proteins