Effect of glycosylated vitamin D binding protein complexed with oleic acid on human myeloma and Hodgkin’s lymphoma cultures

Abstract

N-Acetylgalactosamine-glycosylated vitamin D binding protein (GalNAc-DBP) is known to stimulate macrophages and to directly inhibit angiogenesis and cancer cell growth in vitro. In this study, we evaluated the direct effect of GalNAc-DBP complexed with oleic acid on human multiple myeloma and Hodgkin's lymphoma cell lines (KMS-12-BM and L540 respectively) as well as the effect, on the same cell lines, of human spleen macrophages (CRL9853) previously activated by GalNAc-DBP complexed with oleic acid.Cell viability and living cell number were evaluated respectively by Tetrazolium dye cell viability assay and by Trypan Blue staining. Interactions between activated macrophages and cancer cells were studied by time lapse photography. Our results show that GalNAc-DBP complexed with oleic acid inhibits the proliferation of myeloma and Hodgkin's lymphoma cells in a dose-dependent manner. Furthermore, GalNAc-DBP complexed with oleic acid activates human spleen macrophages which in turn phagocytise cancer cells. In addition, we observed that GalNAc-DBP complexed with oleic acid activates human spleen macrophages in vivo as documented by color-doppler ultrasonography of the spleen. These results demonstrate that GalNAc-DBP complexed with oleic acid has a double effect on myeloma and Hodgkin's lymphoma cancer cells: a direct inhibition of their proliferation and viability and, at the same time, an efficient macrophage activation leading to a significant depletion of cancer cell population. Taken together, these results suggest that GalNAc-DBP complexed with oleic acid may prove effective in the integrative immunotherapy of multiple myeloma and Hodgkin's lymphoma.