Effect of toll-like receptor 3 agonists on the functionality and metastatic properties of breast cancer cell model.

Abstract

There exists compelling evidence that Toll-like receptor 3 (TLR3) agonists can directly affect human cancer cells. The aim of this study was to investigate anti-cancer effects of TLR3 agonist in human breast cell line. We assessed potential effects of poly (A:U) on human breast cell line (MDA-MB-231) on a dose-response and time-course basis. Human breast cell line MDA-MB-231 was treated with different concentrations of poly (A:U) and lipopolysaccharide (LPS). Then, the following assays were performed on the treated cells: dose-response and time-course cytotoxicity using colorimetric method; matrix metalloproteinase-2 (MMP-2) activity using gelatin zymography method; apoptosis using annexin-v flowcytometry method; and relative expression of TLR3 and MMP-2 mRNA using reverse transcriptase polymerase chain reaction (RT-PCR) method. Following treatments, dose- response and time-course cytotoxicity using a colorimetric method, (MMP-2) activity (using gelatin zymography), apoptosis (using annexin-v flowcytometry method) assays and expression of TLR3 and MMP-2 genes (using PCR method) were performed. Cytotoxicity and flowcytometry analysis of poly (A:U) showed that poly (A:U) do not have any cytotoxic and apoptotic effects in different concentrations used. MMP-2 activity analysis showed significant decrease in higher concentrations (50 and 100 μg/ ml) between treated and untreated cells. Moreover, poly A:U treated cells demonstrated decreased expression of MMP-2 gene in higher concentrations. Collectively, our data indicated that human breast cancer cell line (MDA-MB-231) was highly responsive to poly (A:U). The antimetastatic effect of direct poly (A:U) and TLR3 interactions in MDA-MB-231 cells could provide new approaches in malignant tumor therapeutic strategy.

• Authors: Nastaran Alizadeh, Mohammad Mehdi Amiri, Alireza Salek Moghadam, Amir Hassan Zarnani, Farshid Saadat, Farnaz Safavifar, Azar Berahmeh, Mohammad Reza Khorramizadeh
• Journal: Iranian journal of allergy, asthma, and immunology (Iran J Allergy Asthma Immunol) Vol. 12 Issue 2 Pg. 161-7 (May 15 2013) ISSN: 1735-1502 [Print] Iran
• PMID: 23754355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• TLR3 protein, human
• Toll-Like Receptor 3
• Poly A-U
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Apoptosis (drug effects)
• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Female
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Poly A-U (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Toll-Like Receptor 3 (agonists)