Antitumor activity of hydroxythiamine and methotrexate immobilized on monocarboxycellulose.
The aim of the present study was to examine the antitumor and antivitamin activities of some new combinations of methotrexate (MT) and hydroxythiamine (HT), antagonists of folic acid and thiamine, respectively, immobilized on monocarboxycellulose (MCC). Ehrlich ascites carcinoma and sarcoma 180 were used as test malignant tumors in mice. It has been shown, that the compounds studied decreased significantly the amount of mitotically dividing tumor cells and increased the percentage of dead cells, inhibited the tumor growth (up to 10-30 fold at the early stage of neoplasm development) and elongated the life-span of tumor-bearing animals (by 1.6-3.3-fold) as compared to the control. All MCC-immobilized HT and MT complexes studied demonstrated higher antitumor efficacy compared to the mixture of these drugs or each of the agents applied individually. The specific feature of the newly synthesized substances was strong and prolonged antitumor effect following single administration. The severity of thiamine and folic acid deficiencies essentially depended on the amount of HT and MT in the preparations. A close correlation was found between the inhibition of transketolase in the tumors and the antiblastoma properties of the preparations. It enables us to suggest, that the antithiamine action of these preparations is one of the important factors in the mechanism of their antitumor effect.
Zimatkina
T
T
Institute of Biochemistry, Academy of Sciences of Belarus, Grodno, Belarus.
Yurkshtovich
T
T
Zimatkin
S
S
Kaputsky
F
F
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000097:blood / Q000188:drug therapy; D002483:Cellulose, Oxidized; D004906:Erythrocyte Count; D005260:Female; D006452:Hemoglobinometry; D007958:Leukocyte Count; D008727:Methotrexate / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D010119:Oxythiamine / Q000008:administration & dosage* / Q000494:pharmacology; D012510:Sarcoma 180 / Q000097:blood / Q000188:drug therapy
D002483:Cellulose, Oxidized; D010119:Oxythiamine; C585137:6-carboxycellulose; D008727:Methotrexate