Modulation of IKK/NF-κB Signaling: A Therapeutic Mechanism of Shilajit in Breast Cancer Cells

Objective: Although numerous pharmacological effects of Shilajit have been explored by extensive experiments, there is no study on the effects of this ayurvedic substance on the mRNA level of NF-κB family members (p۵۰ and RelB) and IKK subunits (IKKα and β), in breast cancers. Accordingly, the objective of the current experiment was the mechanistic evaluation of the anti-tumoral potential of Shilajit against the breast cancer cell line (MCF-۷). In this experimental study, the viability% of Shilajit (۰, ۱۰۰, ۲۰۰, ۴۰۰, ۶۰۰, and ۸۰۰ μg/mL)-treated cells was analyzed after ۲۴, ۴۸, and ۷۲ h. In the following, the apoptotic rate and p۵۰, RelB, and IKKα/β genes expression were assessed using flow cytometry and real-time PCR assays, respectively.Results: Shilajit had a potent cytotoxic activity in a dose- and time-dependent manner with an IC۵۰ of ۲۸۰ μg/mL. Based on the Annexin-PI analysis, IC۵۰ concentration of this compound induced significant apoptosis in the cells, possibly through suppression of NF-κB-regulated genes. The expression levels exhibited significant (P≤۰.۰۵) downregulation of these genes in the treatment group. The findings of the present experiment clearly indicate that Shilajit possesses promising anti- breast tumor activity through inhibition of IKK/NF-κB signaling pathway.

Keywords:

Shilajit , IκB kinase , Nuclear factor kappa B , breast cancer