Biopolym. Cell. 2024; 40(2):118-126.
Molecular Biomedicine
Oligoribonucleotides in complexes with D-mannitol alter cell cycle and cause apoptosis in murine melanoma B16 cells
1Prylutska I. M., 1Tkachuk Z. Yu.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. Natural oligoribonucleotides in complexes with D-mannitol (ORN-D-M) exhibit cytotoxic effects on various malignant cell lines in a dose- and time-dependent manner. This study aims to elucidate the potential mechanisms underlying the inhibition of mouse melanoma B16 cells viability by ORN-D-M. Methods. Flow cytometry, RT-qPCR. Results. Our findings reveal that ORN-D-M induce cell cycle arrest in the G0/G1 phase and elevate the level of fragmented (apoptotic) DNA. Additionally, we observed the upregulation of RNA receptors Tlr3, Tlr7, Tlr8, and Eif2ak, along with the inflammation-suppressive subunit of transcriptional factor Nfkb1, and the cytokines Ifna and Ifnb, known for their antitumor properties. As a result, the downregulation of inflammatory cytokines Tnfa and Il1b, as well as the changes in apoptotic factors Bcl2, Bax and Casp3 were observed. Conclusions. ORN-D-M induce the cell cycle arrest and apoptosis by promoting extensive production of the inflammation-suppressive subunit NFKB1 and cytokines IFN type I due to the triggering of RNA-sensitive receptors in the cell.
Keywords: ORN-D-M, RNA receptors, relative mRNA level, RT-qPCR, cell cycle

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