Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy
We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cyclespecific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow. [J Natl Cancer Inst 83:1149-1156, 1991]. © 1991 Oxford University Press.
Oredipe, Oladipo A.; White, Sandra L.; Grzegorzewski, Krzysztof; Gause, Barry L.; Cha, Jin K.; Miles, Vitilla A.; and Olden, Kenneth, "Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy" (1991). Howard University Cancer Center Faculty Publications. 219.