Nuclear factor-κB is involved in the protocadherin-10-mediated pro-apoptotic effect in multiple myeloma.

Abstract

The gene encoding protocadherin-10 (PCDH10), a member of the cadherin superfamily, has been recently identified as a tumor suppressor gene (TSG). PCDH10 plays important roles in the apoptosis of tumor cells in some cancer types. However, the exact role of PCDH10 in multiple myeloma(MM) is largely unknown. Increasing evidence has suggested that the activation of nuclear factor-κB(NF-κB) is crucial for apoptosis in myeloma cells. In this study, we investigated the pro-apoptotic effect of PCDH10 on myeloma cells and whether this effect may involve inhibition of the NF-κB pathway. We report here, for the first time to the best of our knowledge, that PCDH10 markedly induces apoptosis of myeloma cells, accompanied by an increase in activated caspase-3 and poly-ADP‑ribose polymerase(PARP) levels, and inhibited expression of anti‑apoptotic proteins. We also demonstrate that PCDH10 inhibits the activation of NF-κB, by inhibiting the expression of the inhibitor of nuclear factor-κB(IκB) kinase subunits(IKKs) and the phosphorylation of IκBα. Moreover, the constitutive NF-κB DNA-binding activity and the expression of the NF-κB‑regulated proteins cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) and intercellular adhesion molecule1(ICAM-1) were inhibited by PCDH10 in MM cells. These results suggest that PCDH10 induces myeloma cell apoptosis, probably by inhibiting the NF-κB pathway.