Effect of arsenic trioxide on cell cycle arrest in head and neck cancer cell line PCI-1.
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.
Seol
J G
JG
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.
Park
W H
WH
Kim
E S
ES
Jung
C W
CW
Hyun
J M
JM
Kim
B K
BK
Lee
Y Y
YY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006131:Growth Inhibitors; D010087:Oxides; D016203:CDC2 Protein Kinase; D000077237:Arsenic Trioxide