부산대학교 도서관

Given the involvement of H2S, a gaseous mediator, in multiple myeloma (MM) cell proliferation and survival, we evaluated effects of benserazide and L-carbidopa, aromatic L-amino acid decarboxylase (AADC) inhibitors capable of inhibiting cystathionine-β-synthase (CBS), an H2S-forming enzyme, on the viability of human MM-derived KMS-11 and bortezomib (BTZ)-resistant KMS-11/BTZ cells. Three different H2S-forming enzymes, i.e. CBS, cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), were comparably expressed in KMS-11 and KMS-11/BTZ cells. Application of BTZ at 10 nM for 24 h upregulated CBS, but not CSE or 3-MST, in KMS-11 cells. Benserazide and L-carbidopa, as well as aminooxyacetic acid, a well-known CBS inhibitor, markedly reduced viability of both MM cells, an effect mimicked by D-carbidopa that inhibited CBS, but not AADC. CSE and 3-MST inhibitors had relatively weak and little anti-MM effects, respectively. The cytotoxic effect of L-carbidopa was reversed by Na2S, an H2S donor. Benserazide and L- and D-carbidopa reduced phosphorylation of NF-κB p65 in KMS-11 cells. Our data suggest that the CBS/H2S/NF-κB pathway is involved in the survival of BTZ-sensitive and -resistant MM, and that D-carbidopa, an inhibitor of CBS, but not AADC, would be useful to treat BTZ-resistant MM.