Sinapine reverses multi-drug resistance in MCF-7/dox cancer cells by downregulating FGFR4/FRS2α-ERK1/2 pathway-mediated NF-κB activation.

Abstract

BACKGROUND:

Sinapine, an alkaloid derived from seeds of the cruciferous species, shows favorable biological properties, such as antioxidant and radio-protective activities. The inhibitory effect of sinapine on acquired chemoresistance in tumor cells and the underlying molecular mechanisms remain unknown.

AIM:

We examined the effect of sinapine on reversal of chemoresistance in Michigan Cancer Foundation 7 (MCF-7)/dox breast cancer cells.

RESULTS:

Combination treatment with sinapine and doxorubicin synergistically increased the cytotoxicity of doxorubicin in MCF-7/dox cells, as shown using a cell apoptosis assay. An accumulation assay demonstrated that sinapine increased the intracellular concentration of doxorubicin in a dose-dependent manner. Immunoblotting and real time polymerase chain reaction (RT-PCR) analysis showed that sinapine downregulated multi-drug resistance 1 (MDR1) expression. A significant correlation was observed between the expression of MDR1, phospho-factor receptor substrate (FRS), phospho-extracellular signal regulated kinase (ERK)1/2, and nuclear factor kappa B (NF-κB). Chromatin immunoprecipitation (ChIP) assay indicated that sinapine inhibited binding of the transcription factor NF-κB to the MDR1 promoter.

CONCLUSIONS:

Our findings indicated that sinapine played an important role in the downregulation of MDR1 expression through suppression of fibroblast growth factor receptor (FGFR)4/FRS2α-ERK1/2 mediated NF-κB activation in MCF-7/dox cancer cells.

• Authors: Ying Guo, Yuanyuan Ding, Tao Zhang, Hongli An
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 23 Issue 3 Pg. 267-73 (Mar 15 2016) ISSN: 1618-095X [Electronic] Germany
• PMID: 26969380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• NF-kappa B
• sinapine
• Doxorubicin
• Choline

Topics

• ATP Binding Cassette Transporter, Subfamily B (metabolism)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Choline (analogs & derivatives, pharmacology)
• Down-Regulation (drug effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Synergism
• Gene Expression Regulation, Neoplastic
• Humans
• MAP Kinase Signaling System (drug effects)
• MCF-7 Cells
• NF-kappa B (metabolism)
• Promoter Regions, Genetic