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

作　　者：LIU Min-Yu XIAO Lin CHEN Geng-Hui WANG Yong-Xiang XIONG Wei-Xia LI Fei LIU Ying HUANG Xiao-Ling DENG Yi-Fang ZHANG Zhen SUN Hai-Yan LIU Quan-Hai YIN Ming 

机构地区：[1]School of Pharmacy, Shanghai Jiao Tong University [2]Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry [3]Beijing Wenfeng Tianji Pharmaceuticals Ltd.

出　　处：《Chinese Journal of Natural Medicines》2014年第10期768-776,共9页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.30973639);the Biomedicine Scientific and Technological Projects of Shanghai(#1043 1900700)

摘　　要：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 μmol·L-1. JS-38(1 μmol·L-1) caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38(15, 30, and 60 mg?kg-1?d-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.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 μmol·L-1. JS-38（1 μmol·L-1） caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38（15, 30, and 60 mg？kg-1？d-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.

关 键 词：JS-38 （mitothiolore） Xenorhabdus sp. Anti-tumor activity NEUTROPHILS Apoptosis 

分 类 号：R965[医药卫生—药理学]