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Indole glucosinolates exhibit anti-inflammatory effects on Ehrlich ascites carcinoma cells through modulation of inflammatory markers and miRNAs

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Abstract

Background

Nuclear factor-κB (NF-κB) has been identified as the major link between inflammation and cancer. Natural agents that inhibit this pathway are essential in attenuating inflammation induced by cancer or chemotherapeutic drugs. High intake of Brassicaceae vegetables has been determined to modulate essential pathways related to chronic diseases. In this study, we investigated the anti-proliferative and anti-inflammatory effects of the indole glucosinolates; indole-3-carbinol (I3C) and its metabolite 3,3-diindolylmethane (DIM) on the inflammatory biomarkers and miRNAs controlling the NF-κB pathway.

Methods and results

In our study, we inoculated Ehrlich ascites carcinoma (EAC) cells in female albino mice, which increased their packed cell volume and induced a significant increase in the levels of several cytokines and inflammatory biomarkers (NF-κB IL-6, IL-1b, TNF-α, and NO). A significant elevation in inflammatory-medicated miRNAs (miR-31 and miR-21) was also noted. Treatment with 5-fluorouracil (5-FU) significantly reduced packed cell volume and viable cell count. However, it was accompanied by a significant increase in the levels of inflammatory markers and expression of miR-31 and miR-21. Nevertheless, although treatment with indoles (I3C and DIM) significantly reduced the packed cell volume and viable cell count, their prominent effect was the marked reduction of all inflammatory biomarkers compared to both the EAC untreated group and the EAC group treated with 5-FU. Moreover, the anti-inflammatory effect of I3C or DIM was accompanied by a significant decrease in the expression of miR-31 and miR-21.

Conclusion

Our findings have; therefore, revealed that I3C and DIM have strong anti-inflammatory effects, implying that their use as a co-treatment with chemotherapeutic drugs can effectively improve the anti-tumor effect of chemotherapeutic drugs.

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All authors mutually agree to forward this manuscript for submission. All authors discussed the results and contributed to the final form of the manuscript. We affirm that the submitted manuscript has not been previously published in any language anywhere and is not submitted for publication elsewhere.

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Funding

This research was partially supported by the National Research Centre, Cairo, Egypt (Grant No. 11010332, PI; Sherien M. El-Daly).

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt

    Ayah Z. Salem, Shadia A. Fathy & Mohamed R. Mohamed

  2. Medical Biochemistry Department, Medical Research Division, National Research Centre, 33 El Buhouth St. Dokki, Cairo, 12622, Egypt

    Dalia Medhat, Zakaria El-Khayat & Sherien M. El-Daly

  3. Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt

    Sherien M. El-Daly

Authors
  1. Ayah Z. Salem
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  2. Dalia Medhat
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  4. Mohamed R. Mohamed
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  5. Zakaria El-Khayat
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  6. Sherien M. El-Daly
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Contributions

El-Daly S.M., Fathy S.A., Mohamed R.M., and El-Khayat Z. developed the idea and planned the work. Salem A.Z., Medhat D., and El-Daly S.M., performed the required experiments. Medhat D., El-Daly S.M., and Salem A.Z. wrote the manuscript in consultation with El-Khayat Z., Fathy S.A., Mohamed R.M. participated in drafting the article and reviewing the manuscript.

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Correspondence to Sherien M. El-Daly.

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All animal procedures of the current protocol were approved by the Animal Ethics Committee of the National Research Centre, Cairo, Egypt.

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Salem, A.Z., Medhat, D., Fathy, S.A. et al. Indole glucosinolates exhibit anti-inflammatory effects on Ehrlich ascites carcinoma cells through modulation of inflammatory markers and miRNAs. Mol Biol Rep 48, 6845–6855 (2021). https://doi.org/10.1007/s11033-021-06683-5

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