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Phenylacetate Induces Growth Inhibition and Apoptosis of Human Osteosarcoma Cells

문우성|이동근|강명재|박호성|장규윤|정명자|Jong Hyuk Park|Min Young Park
대한암학회 (Korean Cancer Association)|2004.10|Cancer Research and Treatment|제36권 제5호|pp. 324-329

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Abstract

Purpose: 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. Materials and 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 p21Cip1 were observed subsequent to treatment with phenylacetate. Conclusion: 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.(Cancer Res Treat. 2004;36:324-329)

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