Effect of monensin liposomes on the cytotoxicity of anti-My9-bR immunotoxin.
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 x 10(-8) M). The combination of anti-My9-bR immunotoxin (50ng mL(-1)) with monensin liposomes (5 x 10(-8) M) 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 microg 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 microg kg(-1)) in combination with monensin liposomes (4 microg 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.
Shaik
Madhu Sudhan
MS
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Jackson
Tanise L
TL
Singh
Mandip
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D000922:Immunotoxins / Q000187:drug effects* / Q000494:pharmacology; D007476:Ionophores / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID; D008985:Monensin / Q000008:administration & dosage / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000922:Immunotoxins; D007476:Ionophores; D008081:Liposomes; D008985:Monensin