Antitumor activity of bestatin and thiorphan in mice.
We have investigated the effect of bestatin and thiorphan on growth of murine transplantable tumors, survival time, activity of natural killer (NK) cells and macrophages in mice. The injections of thiorphan at the does of 0.5 or 5 micrograms per mouse retarded tumor growth and prolonged survival period in B16 melanoma bearing animals. Pretreatment with naloxone (an unspecific antagonist of opioid receptors) blocked the tumor growth inhibition induced by the treatment with bestatin and thiorphan what could suggest a contribution of endogenous enkephalin in this antitumor effect. The percentage of mice bearing B16 melanoma tumor in the group treated with thiorphan at doses of 0.5, 5 or 50 micrograms per mouse was lower in comparison with control animals in a dose-dependent manner. The treatment with thiorphan at concentrations of 0.4-1.6 mg/ml inhibited growth of cultured in vitro B16 melanoma cell in comparison with control culture. Thiorphan added to the medium at concentration of 0.5 microgram/ml or administered 4 times at the dose of 0.5 microgram/mouse augmented NK lymphocyte activity.
Kowalski
J
J
Department of Clinical Pharmacology, Silesian Medical Academy, Katowice, Poland.
Belowski
D
D
Madej
A
A
Herman
Z S
ZS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009270:Naloxone / Q000494:pharmacology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D015244:Thiorphan / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D009270:Naloxone; D015244:Thiorphan; D007930:Leucine; C012211:ubenimex