The designed NF-κB inhibitor, DHMEQ, inhibits KISS1R-mediated invasion and increases drug-sensitivity in mouse plasmacytoma SP2/0 cells

Plasmacytoma is one of the most difficult types of leukemia to treat, and it often invades the bone down to the marrow resulting in the development of multiple myeloma. NF-κB is often constitutively activated, and promotes metastasis and drug resistance in neoplastic cells. The present study assessed the cellular anticancer activity of an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on mouse plasmacytoma SP2/0 cells. Cellular invasion was measured by Matrigel chamber assay, and apoptosis was assessed by detecting caspase-3 cleavage and by flow cytometric analysis with Annexin V. DHMEQ inhibited constitutively activated NF-κB at nontoxic concentrations. DHMEQ was also shown to inhibit cellular invasion of SP2/0 cells, as well as human myeloma KMS-11 and RPMI-8226 cells. The metastasis PCR array indicated that DHMEQ induced a decrease in KISS1 receptor (KISS1R) expression in SP2/0 cells. Knockdown of KISS1R by small interfering RNA suppressed cellular invasion, suggesting that KISS1R may serve an essential role in the invasion of SP2/0 cells. Furthermore, DHMEQ enhanced cytotoxicity of the anticancer agent melphalan in SP2/0 cells. Notably, DHMEQ inhibited the expression of NF-κB-dependent anti-apoptotic proteins, such as Bcl-XL, FLIP, and Bfl-1. In conclusion, inhibition of constitutively activated NF-κB by DHMEQ may be useful for future anti-metastatic and anticancer strategies for the treatment of plasmacytoma.