Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase.

Abstract

Oligomeric ellagitannins (nobotanins B, E, and K) were found to be potent inhibitors of poly(ADP-ribose) glycohydrolase purified from mouse mammary tumor 34I cells. Kinetic analysis revealed that the inhibition of nobotanin B (dimer) was competitive with respect to the substrate poly(ADP-ribose), whereas nobotanin E (trimer) and nobotanin K (tetramer) exhibited mixed-type inhibition. These results suggest that the dimeric structure of ellagitannin may have a functional domain that competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule. To determine the inhibitory effects of oligomeric ellagitannins on poly(ADP-ribose) glycohydrolase in vivo, we examined their effects on de-poly(ADP-ribosyl)ation of some chromosomal proteins in intact 34I cells that was induced by glucocorticoid treatment. Nobotanin B caused concentration-dependent inhibition of glucocorticoid-induced de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in intact 34I cells. Interestingly, this inhibition was associated with suppression of the glucocorticoid-sensitive mouse mammary tumor virus (MMTV) mRNA synthesis. In contrast, nobotanin E and K had little inhibitory effect on either de-poly(ADP-ribosyl)ation of these proteins or induction of MMTV transcription after glucocorticoid treatment. Nobotanin B but not E and K was taken into 34I cells. These results may suggest that the suppression of glucocorticoid-sensitive MMTV transcription results from in vivo inhibition of poly(ADP-ribose) glycohydrolase by nobotanin B. These results also indicate the importance of de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in regulation of transcription of the glucocorticoid-sensitive MMTV gene.

• Authors: Y J Tsai, T Aoki, H Maruta, H Abe, H Sakagami, T Hatano, T Okuda, S Tanuma
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 267 Issue 20 Pg. 14436-42 (Jul 15 1992) ISSN: 0021-9258 [Print] United States
• PMID: 1321148 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrolyzable Tannins
• Tannins
• nobotanin B
• nobotanin E
• nobotanin K
• Glycoside Hydrolases
• poly ADP-ribose glycohydrolase

Topics

• Animals
• Binding, Competitive
• Cell Nucleus (enzymology)
• Gene Expression (drug effects)
• Gene Expression Regulation, Viral (drug effects)
• Genes, Viral (drug effects)
• Glycoside Hydrolases (antagonists & inhibitors, isolation & purification)
• Hydrolyzable Tannins
• Kinetics
• Mammary Neoplasms, Experimental
• Mammary Tumor Virus, Mouse (drug effects, genetics)
• Mice
• Mice, Inbred C3H
• Molecular Structure
• Structure-Activity Relationship
• Tannins (pharmacology)
• Transcription, Genetic
• Tumor Cells, Cultured