Investigation of the anti-inflammatory effect of Indoles on Ehrlich Ascites carcinoma in murine model

Abstract

Nuclear factor-κB (NF-κB) has been identified as the major link between inflammation and cancer. NF-κB controls transcriptional activation of several genes related to inflammation. Natural agents that inhibit this pathway are essential in attenuating inflammation induced by cancer and/or induced by chemotherapeutic drugs. A high intake of Brassicaceae vegetables is linked to a lower incidence of cancer, related to the breakdown of glucosinolates into bioactive indole compounds, suggesting their involvement in modulating essential pathways related to chronic diseases. In the present study, inoculation of Ehrlich ascites carcinoma (EAC) cells in female albino mice resulted in a marked increase in packed cell volume, viable cell count, and a significant increase in the level of NF-κB, in addition to several cytokines and inflammatory biomarkers (IL-6, IL-1b, TNF-α, and NO). A significant elevation in the inflammatory-medicated miRNAs (miR-31 and miR-21) was also detected. Treatment with 5-Fluorouracil (5-FU) significantly reduces packed cell volume and the viable cell count. However, it was accompanied by a significant increase in the levels of inflammatory markers and the expression of miR-31and miR-21 compared to the untreated group. Although treatment with the glucosinolates indoles, indole-3-carbinol (I3C) and 3,3-diindolylmethane (DIM) significantly reduce the packed cell volume and the viable cell count, it was still less effective than 5-FU treatment. On the other hand, I3C and DIM significantly reduced the inflammatory response compared to both EAC inoculated untreated group and the EAC group treated with 5-FU. Moreover, their anti-inflammatory effect was modulated by a significant reduction in the inflammatory-medicated miRNAs (miR-31 and miR-21). Our findings showed that I3C and DIM have a strong anti-inflammatory effect, implying that their use as a co-treatment with chemotherapeutic drugs could effectively improve the anti-tumor effect of chemotherapeutics.