Inhibition of specificity protein 1 by dibenzylideneacetone, a curcumin analogue, induces apoptosis in mucoepidermoid carcinomas and tumor xenografts through Bim and truncated Bid.

Abstract

OBJECTIVES:

Dibenzylideneacetone (DBA), a curcumin analogue that has anti-cancer activity in a variety of tumor cells. In this study, we investigated the apoptotic effects of DBA and its molecular mechanism in human mucoepidermoid carcinoma (MEC) cell lines and tumor xenografts.

MATERIAL AND METHODS:

The apoptotic effects and related molecular mechanisms of DBA on MEC cell lines were evaluated using cell viability assay, DAPI staining, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and Dual-luciferase Reporter Assay. The anti-tumor activity using in vivo were determined by Nude mouse xenograft assay and histopathological examination.

RESULTS:

DBA decreased cell viability and induced apoptosis in MEC cells. These events were accompanied by inhibition of specificity protein 1 (Sp1). DBA did not induce major changes in Sp1 mRNA and promoter activity. Furthermore, inhibition of protein synthesis by cycloheximide demonstrated that DBA decreased Sp1 protein stability, but DBA did not attenuate phosphorylation of eIF4E. DBA also increased Bim and truncated Bid (t-Bid) via Sp1. Finally, DBA exhibited significant anti-tumor activity in athymic nude mice xenografts bearing MC-3 cells by regulating Sp1, Bim and t-Bid without any systemic toxicity.

CONCLUSION:

These results elucidate a crucial apoptotic mechanism of DBA and suggest that DBA may be a potent anticancer drug candidate for MEC.

• Authors: Heang-Eun Lee, Eun-Sun Choi, Ji-Youn Jung, Myung-Jo You, Lee-Han Kim, Sung-Dae Cho
• Journal: Oral oncology (Oral Oncol) Vol. 50 Issue 3 Pg. 189-95 (Mar 2014) ISSN: 1879-0593 [Electronic] England
• PMID: 24309154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• BCL2L11 protein, human
• BH3 Interacting Domain Death Agonist Protein
• Bcl-2-Like Protein 11
• Bcl2l11 protein, mouse
• Biomarkers, Tumor
• Eukaryotic Initiation Factor-4E
• Membrane Proteins
• Pentanones
• Protein Synthesis Inhibitors
• Proto-Oncogene Proteins
• Sp1 Transcription Factor
• Cycloheximide
• dibenzylidene acetone

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Bcl-2-Like Protein 11
• Biomarkers, Tumor (metabolism)
• Carcinoma, Mucoepidermoid (metabolism)
• Cell Line, Tumor
• Cycloheximide (pharmacology)
• Eukaryotic Initiation Factor-4E (metabolism)
• Female
• Humans
• Membrane Proteins (metabolism)
• Mice
• Mice, Nude
• Neoplasms, Experimental
• Pentanones (pharmacology)
• Protein Synthesis Inhibitors (pharmacology)
• Proto-Oncogene Proteins (metabolism)
• Sp1 Transcription Factor (antagonists & inhibitors, metabolism)
• Xenograft Model Antitumor Assays