Effect of monensin liposomes on the cytotoxicity of anti-My9-bR immunotoxin

• Published in: Journal of pharmacy and pharmacology 2003-06, Vol.55 (6), p.819-825
• Main Authors: Shaik, Madhu Sudhan, Jackson, Tanise L., Singh, Mandip
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biological and medical sciences; Female; Immunotoxins - drug effects; Immunotoxins - pharmacology; Ionophores - administration & dosage; Ionophores - pharmacology; Liposomes; Medical sciences; Mice; Mice, SCID; Monensin - administration & dosage; Monensin - pharmacology; Neoplasms - drug therapy; Tumor Cells, Cultured - drug effects
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/002235703765951438

The purpose of the study was to evaluate the utility of monensin liposomes in the enhancement of in‐vitro cytotoxicity, apoptosis and in‐vivo antitumour activity of anti‐My9‐bR immunotoxin. Monensin liposomes were prepared and studied for the enhancement of in‐vitro cytotoxicity and apoptotic response of anti‐My9‐bR immunotoxin against both sensitive and resistant human promyelocytic leukemia HL‐60 cells by MTS/PES method and acridine orange staining, respectively. Further, the in‐vivo cytotoxicity enhancement of anti‐My9‐bR immunotoxin by monensin liposomes was studied in a survival model of severe combined immunodeficient (SCID) mice bearing intraperitoneal HL‐60 tumours. The in‐vitro cytotoxicity of anti‐My9‐bR immunotoxin was enhanced 580 fold and 4.7 fold against sensitive and resistant HL‐60 cells, respectively, by monensin liposomes (5 times 10−8m). The combination of anti‐My9‐bR immunotoxin (50 ng mL−1) with monensin liposomes (5 times 10−8m) produced apoptosis in 40% of cells, whereas the apoptotic response was minimal (< 10%) in anti‐My9‐bR immunotoxin‐ or monensin liposome (alone)‐treated HL‐60 (resistant) cells. In SCID mice bearing HL‐60 tumours, anti‐My9‐bR immunotoxin (75 μg kg−1 administered intravenously every other day for a total of five courses) showed a median survival time of 20 days, which was no different than that of vehicle control‐ or monensin liposome‐treated mice. However, anti‐My9‐bR immunotoxin (75 μg kg−1) in combination with monensin liposomes (4 μg kg−1 monensin), administered every other day for a total of five courses, was found to prolong the survival of 20% of mice for more than 46 days. Our results indicate that, despite anti‐My9‐bR immunotoxin being ineffective in the HL‐60 tumour model, its combination with monensin liposomes could improve the antitumour response.