SWAINSONINE STIMULATION OF THE PROLIFERATION AND COLONY-FORMING ACTIVITY OF MURINE BONE-MARROW

Swainsonine, an indolizidine alkaloid, was recently reported to exhibit both antineoplastic and immunomodulatory activities (Humphries, M. J.; Olden, K. Asparagine-linked oligosaccharides and tumor metastasis. Pharmacol. Ther. 44: 85-105; 1989). In this study, we show that systemically administered swainsonine promoted the proliferation of murine bone marrow (BM) cells. Animals that received swainsonine intravenously exhibited a significant increase (approximately 5-10 fold) in BM cellularity, engraftment efficiency, and colony forming unit activity using in vitro or in vivo assays. BM cells derived from swainsonine-treated animals or treated with swainsonine in vitro also exhibited a 4-5 fold increase in [H-3]-thymidine incorporation, suggesting that a larger fraction of the cells was in the S-phase of the cell cycle. This provides the first evidence that swainsonine, which stimulates the production of cytokines by cells of the immune system, promoted the proliferation of BM progenitor cells. These results suggest that swainsonine could prove valuable in patients undergoing intensive chemoradiotherapy or autologous BM transplantation by decreasing or possibly eliminating leukopenia or myelosuppression often associated with these procedures; it may also be a useful probe to investigate the mechanism of normal hematopoieses.