Arrest of in vivo growth of a solid Leydig cell tumor by prolonged inhibition of mitochondrial protein synthesis.
Oxytetracycline was given by means of chronic i.v. infusion, in amounts which impair specifically mitochondrial protein synthesis, to Wistar rats carrying a solid Leydig cell tumor. The prolonged inhibition of mitochondrial protein synthesis finally results in proliferation arrest of the s.c. growing tumor. As long as the tumor is growing, the energy-generating capacity of the mitochondrial becomes diluted, until it is reduced to a critical level, which results in growth arrest. This cytostatic effect is found after treatment for 8 to 12 days. During this period, the tumor volume increases to an extent comparable to 2 to 3 tumor cell divisions. The proliferation arrest found is, at least after treatment for 3 weeks, reversible. Withdrawal of oxytetracycline results in continuation of tumor growth after a latent period of about 5 days. The data confirm previous observations made in experimental systems about the usefulness of mitochondrial protein synthesis as target for cancer chemotherapy. They support, moreover, the explanation given for the marked prolongation of survival time found in tetracycline-treated patients with a squamous cell carcinoma of the larynx-pharynx. If antineoplastic therapy, based on inhibition of mitochondrial protein synthesis, is considered, the tetracyclines should be the drugs of choice, because their toxic side effects are minimal at dosages which cause tumor proliferation arrest.
D000818:Animals; D007984:Leydig Cell Tumor / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D010118:Oxytetracycline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology
D009363:Neoplasm Proteins; D010118:Oxytetracycline