Oral JS-38, a metabolite from Xenorhabdus sp., has both anti-tumor activity and the ability to elevate peripheral neutrophils.
10.1016/S1875-5364(14)60117-5
- Author:
Min-Yu LIU
1
,
2
;
Lin XIAO
3
;
Geng-Hui CHEN
4
;
Yong-Xiang WANG
5
;
Wei-Xia XIONG
3
;
Fei LI
3
;
Ying LIU
3
;
Xiao-Ling HUANG
3
;
Yi-Fang DENG
3
;
Zhen ZHANG
3
;
Hai-Yan SUN
3
;
Quan-Hai LIU
6
;
Ming YIN
7
Author Information
1. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
2. Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
3. Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
4. Beijing Wenfeng Tianji Pharmaceuticals Ltd., Beijing 100027, China.
5. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
6. Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China. Electronic address: liuquanhai_lqh@163.com.
7. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: myin@sjtu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Anti-tumor activity;
Apoptosis;
JS-38 (mitothiolore);
Neutrophils;
Xenorhabdus sp.
- MeSH:
Animals;
Antineoplastic Agents;
administration & dosage;
metabolism;
Cell Count;
Female;
Humans;
Hydrocarbons, Fluorinated;
administration & dosage;
metabolism;
Lung Neoplasms;
drug therapy;
physiopathology;
Mice;
Mice, Inbred BALB C;
Mice, Inbred ICR;
Neutrophils;
cytology;
drug effects;
Xenorhabdus;
chemistry;
metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2014;12(10):768-776
- CountryChina
- Language:English
-
Abstract:
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.
