The indolizidine alkaloid, swainsonine, has previously attracted interest for its potential as an anticancer agent with reports that it 1) inhibits tumor growth and metastasis, 2) augments natural killer- and macrophage- mediated tumor cell killing, and 3) stimulates bone marrow cell proliferation. The objective of this study is to determine the potential clinical utility of this compound as a done marrow proliferative agent. An in vitro clonal assay for murine hematopoietic progenitor cells was used to examine the effect of swainsonine on the toxicity of chemotherapeutic agents. Preliminary results with nontumor bearing mice indicate that swainsonine can be used to prevent the toxic effect on bone marrow of drugs such as methotrexate and 5-fluorouracil. We are preparing to test the effects of swainsonine on bone marrow cell proliferation and immune system functions in tumor bearing animals. Additional in vivo studies have performed to ascertain the optimal dosage and time course of administration of swainsonine for maximum protective effect. Further studies are planned to characterize the effect of swainsonine on other chemotherapeutic drugs and to optimize the regimen of administration of swainsonine.
