Anti-tumor protection induced in mice by fatty acid conjugates: alkyl butyrates and poly(ethylene glycol) dibutyrates.
Simple fatty acids, especially butyrate salts, have interesting biological properties, since they are able to down-regulate cell growth and promote various differentiated cellular functions. Their use for anti-tumor treatment is, however, hampered by their over-rapid diffusion in the blood, followed by a short-lived biological action. We have therefore devised conjugates linking butyrate with either (i) aliphatic alcohols of increasing carbon numbers ranging from C4 to C12 or (ii) poly(ethylene glycols) of increasing molecular weights. In both cases, the resulting butyric esters can be hydrolysed by esterases which can release biologically active subunits from the synthetic compounds. As shown in the present study, only one conjugate in each series gave satisfactory anti-tumor protection: namely, I-octyl butyrate and poly(ethylene glycol 1000) dibutyrate respectively. A single immune-stimulatory injection of purified Corynebacterium parvum extract prior to administration of the conjugates significantly increased the anti-tumor potency.
C.N.R.S.-C.E.R.C.O.A, Thiais, France.
M
M
Wakselman
I
I
Cerutti
C
C
Chany
D000276:Adjuvants, Immunologic; D000438:Alcohols / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents; D002087:Butyrates / Q000138:chemical synthesis / Q000494:pharmacology*; D004337:Drug Carriers; D004950:Esterases / Q000378:metabolism; D004951:Esterification; D005026:Ethylene Glycols / Q000138:chemical synthesis / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008970:Molecular Weight; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000276:immunology
D000276:Adjuvants, Immunologic; D000438:Alcohols; D000970:Antineoplastic Agents; D002087:Butyrates; D004337:Drug Carriers; D005026:Ethylene Glycols; D005227:Fatty Acids; D004950:Esterases