Effect of arsenic trioxide on cell cycle arrest in head and neck cancer cell line PCI-1

Arsenic trioxide (As2O3) has been shown to inhibit the proliferation of hem atologic malignant cells. However, little is known about the effect of As2O 3 on solid tumor. In this study, we investigated the antitumoral effect of As2O3 on head and neck cancer cell lines in vitro. Treatment of As2O3 inhib ited the proliferation of all of 4 cell lines examined in a dose-dependent manner. To address the mechanism of antitumoral effect of As2O3, cell cycle analysis was attempted in As2O3-most sensitive PCI-1 cells. Treatment of A s2O3 (2 mu M) induced efficiently G2/M arrest in PCI-1 cells following 3 da ys of exposure. During the G2/M arrest, cyclin-dependent kinase inhibitor, p21, was increased in a time-dependent manner. Analysis of cell cycle regul atory proteins demonstrated that As2O3 (2 mu M) did not change the steady-s tate levels of CDK2, CDK4, CDK6, cyclin D1, cyclin E and cyclin A, but decr eased the protein levels of cdc2 and cyclin B1. Furthermore, treatment of A s2O3 markedly enhanced the binding of p21 with cdc2, and the activity of cd c2 kinase was decreased in a time-dependent manner. These results suggest t hat As2O3 inhibits the proliferation of head and neck cancer cells via G2/M arrest in association with the induction of p21 and the reduction of cdc2 kinase activity. (C) 1999 Academic Press.