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Investigation of the TLR4 and IRF3 signaling pathway-mediated effects of monensin in colorectal cancer cells

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Abstract

Monensin is an ionophore antibiotic isolated from Streptomyces cinnamonensis with very strong antibacterial and antiparasitic effects. Although monensin is known to exhibit anticancer activity in different cancer types, there are a very limited number of studies on its anti-inflammatory effects in colorectal cancer (CRC) cells. The aim of this study was to investigate the TLR4/IRF3-mediated antiproliferative and anti-inflammatory effects of monensin in colorectal cancer cells. The dose- and time-dependent antiproliferative activity of monensin in colorectal cancer cells was determined by XTT method and its effects on mRNA expression changes of Toll-like receptors and IRF3 genes were determined by RT-PCR. TLR4 and Interferon Regulatory Factor 3 (IRF3) protein expression was evaluated by immunofluorescence method. TLR4 and type 1 interferon (IRF) levels were also evaluated by ELISA. IC50 value of monensin in HT29 cells was determined as 10.7082 µM at 48 h and 12.6288 µM at 48th for HCT116 cells. Monensin treatment decreased TLR4 and TLR7 and IRF3 mRNA expression in CRC cells. Monensin treatment decreased the expression level of IRF3 induced by LPS. Our study demonstrates for the first time the TLR4/IRF3-mediated anti-inflammatory effects of monensin in colorectal cancer cells. Further studies on the effects of monensin on TLR receptors in colorectal cancer cells are needed.

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Data availability

The datasets generated and analyzed during the current study are available from the authors on reasonable request.

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Funding

This research was supported by the Scientific Research Coordinatorship of Balıkesir University as the project numbered BAP-2021/072.

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Authors and Affiliations

  1. School of Medicine, Department of Medical Biology, Ordu University, Ordu, Turkey

    Mücahit Seçme

  2. School of Medicine, Department of Histology and Embryology, Balikesir University, Balikesir, Turkey

    Sema Serter Kocoglu

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  1. Mücahit Seçme
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Contributions

MS contributed to conception, design, in vitro experiments, interpretation of data, writing of the paper, and final approval. SSK contributed to hypothesis, in vitro experiments, interpretation of data, and final approval.

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Correspondence to Mücahit Seçme.

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Seçme, M., Kocoglu, S.S. Investigation of the TLR4 and IRF3 signaling pathway-mediated effects of monensin in colorectal cancer cells. Med Oncol 40, 187 (2023). https://doi.org/10.1007/s12032-023-02055-0

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