[The cytotoxicity of mevalonate, lovastatin and carminomycin with respect to MOLT-4 human malignant T-lymphoblasts in vitro].
It was shown in vitro that high concentrations of lovastatin, a competitive inhibitor of hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibited human malignant cells MOLT-4. The activity of lovastatin in doses of 50-250 microM was dose-dependent. Addition of mevalonate in a concentration of 3 mM to the growth medium completely prevented the cytotoxic effect of 100 microM of lovastatin. At the same time, exogenous mevalonate did not decrease the cytotoxicity of the anthracycline antibiotic carminomycin. Moreover, in a high concentration (7 mM) mevalonate slowly but significantly inhibited the growth of the malignant target cells and the effect was added to the cytotoxic effect of carminomycin low concentrations (0.08 to 0.175 microgram/ml). The results and the literature data suggested that combination of mevalonate, HMG-CoA reductase inhibitors and anthracyclines could be useful in tumor chemotherapy. The suggestion needs further investigation.
Leont'eva
O V
OV
Institute of New Antibiotics, Russian Academy of Medical Sciences, Moscow.
Trenin
A S
AS
Bukhman
V M
VM
Dudnik
Iu V
IuV
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D002360:Carubicin / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008148:Lovastatin / Q000633:toxicity*; D008798:Mevalonic Acid / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008148:Lovastatin; D002360:Carubicin; D008798:Mevalonic Acid