Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner

Aaptamine, a benzonaphthyridine alkaloid was isolated from a marine sponge on the guidance of a bioassay using the transfected human osteosarconra MG63 cells (MG63luc(+)). Aaptamine activated p21 promoter stably transfected in MG63 cells dose-dependently at the concentrations of 20-50 mu M. Expression of p21 and its mRNA in the wild-type MG63 cells also increased by aaptamine-treatment. Furthermore, the cell cycle of MG63 cells was arrested at the G2/M phase within 48 h by the aaptamine-treatment. To analyze a responive element of p21 promoter in the up-regulation of p21 by aaptamine, MG63 cells were transiently transfected with a series of the deleted or mutated promoter segments; and induction of luciferase with aaptamine treatment was examined by using these corresponding transfected cells. The activation of p21 promoter by aaptamine was led through acting Sp1 sites between -82 and -50 by in a p53-independent manner. (c) 2006 Elsevier Inc. All rights reserved.