RRC ID 41584
Author Zhao S, Tsuchida T, Kawakami K, Shi C, Kawamoto K.
Title Effect of As2O3 on cell cycle progression and cyclins D1 and B1 expression in two glioblastoma cell lines differing in p53 status.
Journal Int J Oncol
Abstract Recent clinical studies have demonstrated that As2O3 is an effective drug in the treatment of acute promyelocytic leukemia (APL) by inducing apoptosis and inhibiting the proliferation of leukemia cells both in vitro and in vivo. As a novel anticancer agent for the treatment of solid cancer, As2O3 is promising, but no experimental investigations of its efficacy on glioblastoma have been conducted at concentrations that may be achieved clinically. In addition, the cell proliferation and cell cycle regulating mechanism of As2O3 has not yet to be clarified, especially in solid cancers. We investigated the effect of As2O3 on proliferation and cell cycle regulation with change in cyclins in two human glioblastoma cell lines differing in p53 status (U87MG-wt; T98G-mutated). Sensitivity to As2O3 varied depending on the dose with the IC50 of the U87MG and T98G cells being 1.78 and 3.55 microM, respectively. Analysis by laser scanning cytometry (LSC) indicated that As2O3 inhibited the proliferation of the two cell lines via cell cycle arrest both at the G1 and G2 phases. To address the mechanism of the antiproliferative effect of As2O3, we examined its effect on cell cycle-related proteins by means of LSC, confocal microscopy and Western blot analysis. As2O3 induced an increase in p53 level and a decrease in level of cyclin B1 combined with cell arrest at G2/M in both cell lines. Cell arrest in G1, however, was associated with a decline in cyclin D1 expression only in the wt U87MG cells. As2O3 also induced apoptosis of U87MG cells as evidenced by the presence of cells with fractional DNA content ( cell populations). The present evidence that As2O3 at relatively low concentration effectively inhibited proliferation of U87MG and T98G cells in vitro, suggests that the drug may be considered for in vivo testing on animal models and possibly clinical trials on glioma patients.
Volume 21(1)
Pages 49-55
Published 2002-7-1
PMID 12063549
MeSH Arsenic Trioxide Arsenicals / pharmacology* Blotting, Western Brain Neoplasms / drug therapy Brain Neoplasms / metabolism* Brain Neoplasms / pathology Cell Cycle / drug effects* Cell Division / drug effects Cyclin B / metabolism* Cyclin B1 Cyclin D1 / metabolism* Dose-Response Relationship, Drug Flow Cytometry Glioblastoma / drug therapy Glioblastoma / metabolism* Glioblastoma / pathology Humans Oxides / pharmacology* Tumor Cells, Cultured / drug effects* Tumor Cells, Cultured / metabolism Tumor Suppressor Protein p53 / metabolism*
IF 3.899
Times Cited 62
Human and Animal Cells