Abstract
Background: Nuclear factor-κB (NF-κB) is the major link between inflammation and cancer. 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 modulating essential pathways related to chronic diseases. In the present study, we investigated the anti-proliferative and anti-inflammatory effect of glucosinolates indoles; indole-3-carbinol (I3C) and 3,3-diindolylmethane (DIM) on the inflammatory biomarkers and miRNAs controlling the NF-κB pathway. Methods and Results: inoculation of Ehrlich ascites carcinoma (EAC) cells in female albino mice resulted in a marked increase in packed cell volume and a significant increase in the level of several cytokines and inflammatory biomarkers (NF-κB 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-31 and miR-21. Although treatment with indoles significantly reduced the packed cell volume and the viable cell count, their most prominent effect was the marked reduction of all inflammatory biomarkers compared to both EAC untreated group and the EAC group treated with 5-FU. Moreover, their anti-inflammatory effect was modulated by a significant decrease in miR-31 and miR-21. Conclusion: Our findings revealed 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 chemotherapies.