title: Oral JS-38, a metabolite from Xenorhabdus sp., has both anti-tumor activity and the ability to elevate peripheral neutrophils.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Beijing Wenfeng Tianji Pharmaceuticals Ltd., Beijing 100027, China.
authors.forename: Geng-Hui
authors.initials: GH
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Deng
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China. Electronic address: liuquanhai_lqh@163.com.
authors.forename: Quan-Hai
authors.initials: QH
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: myin@sjtu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D002452:Cell Count; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D020593:Xenorhabdus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006845:Hydrocarbons, Fluorinated; C533647:JS-38 compound
keywords: Anti-tumor activity; Apoptosis; JS-38 (mitothiolore); Neutrophils; Xenorhabdus sp.