A synthetic uracil derivative with antitumor activity through decreasing cyclin D1 and Cdk1, and increasing p21 and p27 in MCF-7 cells

作者：Marchal Juan A; Nunez Maria C; Suarez Ines; Diaz Gavilan Monica; Gomez Vidal Jose A; Boulaiz Houria; Rodriguez Serrano Fernando; Gallo Miguel A; Espinosa Antonio; Aranega Antonia; Campos Joaquin M^*

来源：Breast Cancer Research and Treatment, 2007, 105(3): 237-246.

DOI：10.1007/s10549-006-9450-2

• breast cancer
• cyclin D1
• Cdk1
• MCF-7
• p21
• p27
• uracil derivative

The anticarcinogenic potential of (RS)-1( 2,3-dihydro-5H-1,4-benzodioxepin-3-yl) uracil (DBDU), with the naturally occurring pyrimidine base uracil, is reported against the MCF-7 cancer cell line. The arrest in the G(0)/G(1) and G(2)/M cell cycle phases was accounted for by decrease in the expression of the cyclin D1 and Cdk1 proteins, and increase in p21 and p27 proteins. Using a reverse transcription-polymerase chain reaction-based assay at a dose of 5 mu M of DBDU cyclin D1 mRNA was decreased, suggesting that DBDU exerts its regulatory action on cyclin D1 at the level of transcription. DNA fragmentation was performed and demonstrated that apoptosis occurred in the tumor cell line treated with DBDU. The G(0)/G(1) arrest is an irreversible process and the cells undergo apoptosis in a p53-independent manner. DBDU administered intravenously twice a week (50 mg/kg dose each time) induced neither toxicity nor death in mice for 5 weeks.

• 出版日期2007-11