Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells
Purpose: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30493 |
| _version_ | 1797726710864543744 |
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| author | Gamze Güney Eskiler Asuman Deveci Özkan Süleyman Kaleli Cemil Bilir |
| author_facet | Gamze Güney Eskiler Asuman Deveci Özkan Süleyman Kaleli Cemil Bilir |
| author_sort | Gamze Güney Eskiler |
| collection | DOAJ |
| description | Purpose: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated. For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. Methods: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay. The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. Results: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-α/β) levels induced by LPS. However, curcumin was more efficient in MDA-MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS- enhanced TLR4 signaling pathway. Furthermore, IFN-α/β levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. Conclusions: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin’s anti-inflammatory activities on TLR4/MyD88/NF-κB as well as other signaling pathways downstream of TLRs in breast cancer. |
| first_indexed | 2024-03-12T10:49:17Z |
| format | Article |
| id | doaj.art-1f79a51e30534bbdaee02f3176995d2e |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2024-03-12T10:49:17Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-1f79a51e30534bbdaee02f3176995d2e2023-09-02T07:07:37ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262019-07-0122110.18433/jpps30493Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer CellsGamze Güney Eskiler0Asuman Deveci Özkan1Süleyman Kaleli2Cemil Bilir3Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.Department of Medical Oncology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.Purpose: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated. For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. Methods: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay. The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. Results: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-α/β) levels induced by LPS. However, curcumin was more efficient in MDA-MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS- enhanced TLR4 signaling pathway. Furthermore, IFN-α/β levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. Conclusions: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin’s anti-inflammatory activities on TLR4/MyD88/NF-κB as well as other signaling pathways downstream of TLRs in breast cancer.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30493 |
| spellingShingle | Gamze Güney Eskiler Asuman Deveci Özkan Süleyman Kaleli Cemil Bilir Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells Journal of Pharmacy & Pharmaceutical Sciences |
| title | Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells |
| title_full | Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells |
| title_fullStr | Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells |
| title_full_unstemmed | Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells |
| title_short | Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells |
| title_sort | inhibition of tlr4 trif irf3 signaling pathway by curcumin in breast cancer cells |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30493 |
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