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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells

Authors: Padmamalini Thulasiraman, Daniel J McAndrews, Imran Q Mohiudddin

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

A major obstacle in the use of retinoid therapy in cancer is the resistance to this agent in tumors. Retinoic acid facilitates the growth of mammary carcinoma cells which express high levels of fatty acid-binding protein 5 (FABP5). This protein delivers retinoic acid to peroxisome proliferator-activated receptor β/δ (PPARβ/δ) that targets genes involved in cell proliferation and survival. One approach to overcome resistance of mammary carcinoma cells to retinoic acid is to target and suppress the FABP5/ PPARβ/δ pathway. The objective of this research was to investigate the effect of curcumin, a polyphenol extract from the plant Curcuma longa, on the FABP5/ PPARβ/δ pathway in retinoic acid resistant triple negative breast cancer cells.

Methods

Cell viability and proliferation of triple negative breast cancer cell lines (MDA-MB-231 and MD-MB-468) treated with curcumin and/or retinoic was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2’-deoxyuridine (BrdU). Expression level of FABP5 and PPARβ/δ in these cells treated with curcumin was examined by Western Blotting analysis and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Effect of curcumin and retinoic acid on PPARβ/δ target genes, PDK1and VEGF-A were also examined using qRT-PCR. Western Blotting was utilized to examine the protein expression level of the p65 subunit of NF-κB.

Results

Treatment of retinoic acid resistant triple negative breast cancer cells with curcumin sensitized these cells to retinoic acid mediated growth suppression, as well as suppressed incorporation of BrdU. Further studies demonstrated that curcumin showed a marked reduction in the expression level of FABP5 and PPARβ/δ. We provide evidence that curcumin suppresses p65, a transcription factor known to regulate FABP5. The combination of curcumin with retinoic acid suppressed PPARβ/δ target genes, VEGF-A and PDK1.

Conclusions

Curcumin suppresses the expression level of FABP5 and PPARβ/δ in triple negative mammary carcinoma cells. By targeting the FABP5/PPARβ/δ pathway, curcumin prevents the delivery of retinoic acid to PPARβ/δ and suppresses retinoic acid-induced PPARβ/δ target gene, VEGF-A. Our data demonstrates that suppression of the FABP5/ PPARβ/δ pathway by curcumin sensitizes retinoic acid resistant triple negative breast cancer cells to retinoic acid mediated growth suppression.
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Metadata
Title
Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells
Authors
Padmamalini Thulasiraman
Daniel J McAndrews
Imran Q Mohiudddin
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-724

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