Phenylacetate induces growth inhibition and apoptosis of human osteosarcoma cells.
OBJECTIVE
Phenylacetate has potent antiproliferative effects in many malignant tumors. However, the exact mechanism as to how phenylacetate induces cell growth arrest remains unclear and very little is known about its effects on human osteosarcoma cells. In this study, we investigated whether phenylacetate is effective against two osteosarcoma cell lines (HOS and U-2 OS) in vitro.


METHODS
The viability of phenylacetate-treated cell lines was assessed by trypan blue exclusion assay, and the cell cycle distribution was measured by flow cytometry. To measure cell apoptosis, poly (ADP-ribose) polymerase cleavage assay and flow cytometry were employed. The expressions of cell cycle-regulatory proteins and the apoptosis-related genes were evaluated by western blot analysis.


RESULTS
Phenylacetate was found to inhibit the growth of osteosarcoma cells, induce cell cycle arrest in the G1 phase, and induce apoptosis. A significant decrease in Bcl-2 expression and a mild up-regulation of Bax were also observed in both phenylacetate-treated cell lines. Reduced phosphorylation of the pRb and the increased expression of p21(Cip1) were observed subsequent to treatment with phenylacetate.


CONCLUSIONS
These findings support the idea that phenylacetate may be an effective chemotherapeutic agent to be employed in the future against osteosarcoma, because phenylacetate acts to inhibit the growth of osteosarcoma cells through cell cycle arrest and apoptosis.
Park
Jong Hyuk
JH
Department of Pathology, Chonbuk National University Medical School, Jeonju, Korea.
Park
Min Young
MY
Park
Ho Sung
HS
Jang
Kyu Yun
KY
Chung
Myoung Ja
MJ
Moon
Woo Sung
WS
Lee
Dong Geun
DG
Kang
Myoung Jae
MJ