Effect of arsenic trioxide on cell cycle arrest in head and neck cancer cell line PCI-1
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1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.
Abstract:
Arsenic trioxide (As(2)O(3)) has been shown to inhibit the proliferation of hematologic malignant cells. However, little is known about the effect of As(2)O(3) on solid tumor. In this study, we investigated the antitumoral effect of As(2)O(3) on head and neck cancer cell lines in vitro. Treatment of As(2)O(3) inhibited the proliferation of all of 4 cell lines examined in a dose-dependent manner. To address the mechanism of antitumoral effect of As(2)O(3), cell cycle analysis was attempted in As(2)O(3)-most sensitive PCI-1 cells. Treatment of As(2)O(3) (2 microM) induced efficiently G2/M arrest in PCI-1 cells following 3 days of exposure. During the G2/M arrest, cyclin-dependent kinase inhibitor, p21, was increased in a time-dependent manner. Analysis of cell cycle regulatory proteins demonstrated that As(2)O(3) (2 microM) did not change the steady-state levels of CDK2, CDK4, CDK6, cyclin D1, cyclin E and cyclin A, but decreased the protein levels of cdc2 and cyclin B1. Furthermore, treatment of As(2)O(3) markedly enhanced the binding of p21 with cdc2, and the activity of cdc2 kinase was decreased in a time-dependent manner. These results suggest that As(2)O(3) 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.
Insights
Arsenic trioxide (As(2)O(3)) effectively inhibits head and neck cancer cell growth by inducing G2/M cell cycle arrest. This occurs through p21 induction and decreased cdc2 kinase activity, revealing its antitumoral mechanism.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Arsenic trioxide (As(2)O(3)) is known for inhibiting hematologic malignancies.
- Its effects on solid tumors, particularly head and neck cancers, are less understood.
Purpose of the Study:
- To investigate the in vitro antitumoral effects of As(2)O(3) on head and neck cancer cell lines.
- To elucidate the underlying molecular mechanisms of As(2)O(3)'s anti-cancer activity.
Main Methods:
- Cell proliferation assays on four head and neck cancer cell lines.
- Cell cycle analysis using flow cytometry.
- Western blot analysis of cell cycle regulatory proteins (p21, cdc2, cyclin B1, etc.).
- Assessment of cdc2 kinase activity and p21 binding to cdc2.
Main Results:
- As(2)O(3) inhibited proliferation in all tested cell lines in a dose-dependent manner.
- As(2)O(3) treatment induced G2/M cell cycle arrest in PCI-1 cells.
- Increased p21 levels and enhanced binding of p21 to cdc2 were observed.
- Decreased protein levels of cdc2 and cyclin B1, along with reduced cdc2 kinase activity, were noted.
Conclusions:
- As(2)O(3) exhibits significant antitumoral effects on head and neck cancer cells in vitro.
- The mechanism involves G2/M cell cycle arrest mediated by p21 induction and inhibition of cdc2 kinase activity.
