Polymyxin B-mediated lysis of tumor cells

Polymyxin B (PmB) in the concentration range of 10-50 micrograms/ml is used routinely in immunological studies to neutralize low levels of contaminating lipopolysaccharide (LPS) in media or reagents. While using PmB for such a purpose unexpected results were obtained, which led to the finding that low levels of PmB are cytotoxic to certain tumor cells. Further examination of a panel of 10 tumor cell lines revealed that in an 18-hour 51Cr release assay, EL4 cells and EL4/ADM cells were very sensitive (lysed by > or = 10 micrograms PmB/ml), C1498 cells and REH cells were moderately sensitive (lysed by > or = 20 micrograms PmB/ml) and cells of the remaining 6 lines were resistant (lysed only by 100 micrograms/ml) to PmB. A similar pattern of sensitivity was observed when 3H-thymidine incorporation was used as a measure of PmB effects in cell proliferation. The PmB concentration needed to kill 50% of the tumor cells in a suspension differed greatly among lines; thus for cells of a resistant line 8-fold more PmB was required for 50% killing than for those of a sensitive line. PmB toxicity toward EL4 cells was shown to increase to a plateau level with increasing time of exposure; however, the higher the concentration the earlier the plateau was reached. LPS may prevent PmB toxic effects since PmB binds to the lipid A portion of the LPS molecule, but 100 micrograms LPS/ml was only able to reduce the toxicity of 10 and 20 micrograms PmB/ml, and not that of 50 or 100 micrograms PmB/ml.(ABSTRACT TRUNCATED AT 250 WORDS)