Oral JS-38,a metabolite from Xenorhabdus sp.,has both anti-tumor activity and the ability to elevate peripheral neutrophils

AIM:JS-38(mitothiolore),a synthetic version of a metabolite isolated from Xenorhabdus sp.,was evaluated for its anti-tumor and white blood cell(WBC) elevating activities.METHOD:These anti-proliferative activities were assessed in vitro using a panel of ten cell lines.The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice.The anti-tumor interactions of JS-38 and cyclophosphamide(CTX) or 5-fluorouracil(5-Fu) were studied in a S180 sarcoma model in ICR mice.Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX-and 5-Fu-induced neutropenic mice.RESULTS:The IC50 values ranged from 0.1 to 2.0 molL-1.JS-38(1 molL-1) caused an increase in A549 tumor cell apoptosis.Multi-daily gavage of JS-38(15,30,and 60 mgkg-1d-1) inhibited in vivo tumor progression without a significant effect on body weight.JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu.JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor(G-CSF).In mice with neutropenia induced by CTX or 5-Fu,JS-38 rapidly restored neutrophil counts.CONCLUSION:These results suggest that JS-38 has anti-tumor activity,and also has the ability to increase peripheral blood neutrophils.