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

Abstract

Aaptamine, a benzonaphthyridine alkaloid was isolated from a marine sponge on the guidance of a bioassay using the transfected human osteosarcoma MG63 cells (MG63luc(+)). Aaptamine activated p21 promoter stably transfected in MG63 cells dose-dependently at the concentrations of 20-50microM. 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 48h by the aaptamine-treatment. To analyze a responsive 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 -50bp in a p53-independent manner.

• Authors: Shunji Aoki, Dexin Kong, Hideaki Suna, Yoshihiro Sowa, Toshiyuki Sakai, Andi Setiawan, Motomasa Kobayashi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 342 Issue 1 Pg. 101-6 (Mar 31 2006) ISSN: 0006-291X [Print] United States
• PMID: 16480688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Naphthyridines
• RNA, Messenger
• Tumor Suppressor Protein p53
• aaptamine

Topics

• Animals
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Gene Deletion
• Gene Expression Regulation (drug effects)
• Genes, Reporter (genetics)
• Humans
• Molecular Structure
• Mutation (genetics)
• Naphthyridines (chemistry, pharmacology)
• Porifera (chemistry, metabolism)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics)
• Tumor Suppressor Protein p53 (metabolism)