Natural oligoribonucleotides in complex with D-mannitol (ORN-D-M) exhibit a range of biological activities, including antiviral and antioxidant effects. In previous investigations, we observed that ORN-D-M demonstrated cytotoxicity on various malignant cell lines in a dose- and time-dependent manner. The aim of the current work was to determine the possible mechanisms of melanoma B16 cell inhibition by ORN-D-M. For this investigation, we examined the relative mRNA expression of various RNA sensors and their downstream-regulated pathways after ORN-D-M treatment of mouse melanoma B16 cells.

It was shown that ORN-D-M caused overexpression of ss-, dsRNA receptors Tlr3, 7, 8, and Eif2ak; the inflammation-suppressive subunit Nfkb1; and IFN type 1. Along with this, downregulation was observed in the mRNA expression of inflammatory cytokines Tnfa and Il1b, which are known as promoters of tumor progression. The ORN-D-M treatment affected apoptosis regulatory molecules, significantly decreasing the relative mRNA level of the antiapoptotic Bcl-2, and slightly increasing proapoptotic Bax.

Therefore, ORN-D-M can be an agonist to Tlr and Eif2ak receptors in melanoma cancer cells, causing the activation of proapoptotic signals through the Nfkb1-dependent pathway.