Isolation and purification of phosphate dependent glutaminase from sarcoma-180 tumor and its antineoplastic effects on murine model system.
High rate of glutamine use is a characteristic of tumor cell both in vivo and in vitro and experimental cancer therapies have developed by depriving tumor cells of glutamine. In several investigations, bacterial glutaminase was found to be a potent therapeutic agent against varieties of tumor, but it showed suppressive effects on haematopoietic systems and inhibitory effects on normal lymphocytic blastogenesis. No antineoplastic study has nevertheless been undertaken with glutaminase enzyme purified from mammalian source. In the present study we report the purification of glutaminase enzyme from mitochondria of highly malignant S-180 cell using ion exchange chromatography and affinity column chromatography of glutamine. Purified enzyme is a kidney type phosphate dependent glutaminase with Mr 64 KD. Effect of enzyme therapy has been investigated in transplantable as well as induced tumor model in both ascites and solid form. It has been observed that the enzyme at the total dose of 10 unit/mouse successfully inhibited the tumor burden both in ascitic and solid tumor and subsequently increases the host's life span. There was no significant toxic effect on the peripheral blood cells.
Maity
P
P
Dept. of Metabolic Regulation, Chittaranjan National Cancer Institute, Calcutta, India.
Chakraborty
S
S
Bhattacharya
P
P
Sarkar
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D005972:Glutaminase / Q000302:isolation & purification* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000201:enzymology*; D014461:Ultracentrifugation
D000970:Antineoplastic Agents; D005972:Glutaminase