DNIC (Nitric Oxide Donor) Suppresses the Expression of Matrix Metalloproteinase and Poly(ADP-ribose)polymerase Genes in Human Multiple Myeloma Cells

Poly(ADP-ribose)polymerase plays an important role in various cell death mechanisms: necrosis, autophagy, and parthanatos. Elevated levels of matrix metalloproteinases correlate with tumor invasiveness and metastasis. Therefore, searching for MMP and PARP inhibitors is important for developing new anticancer drugs. The effect of DNIC#7 (3.9 x 10-4M) on the expression of poly(ADP-ribose)polymerase (PARP-1 and PARP-2) isoenzyme genes in human multiple myeloma cells was studied. It was shown that DNIC#7 suppresses the expression of PARP-1 genes by 50% but activates the expression of PARP-2 genes by 4.5 times. The influence of DNIC#7 on the expression of matrix metalloproteinase (MMP-7, MMP-9) isoenzyme genes in human multiple myeloma cells was studied. RT-PCR showed that DNIC#7 (at a concentration of 3.9 x 10-4 M) suppressed the expression of MMP-7 genes by ~12 times and MMP-9 by 10 times. The results showed that DNIC#7 is an effective inhibitor of PARP-1, MMP-7, and MMP-9. Therefore, DNIC#7 has antitumor potential for treating human multiple myeloma.