Teraphtal decreased the sensitivity tumor cells to doxorubicine in vitro but does not affect its antitumor effect in vivo .

Abstract

Introduction . Anthracycline antibiotic doxorubicin (DOX) is widely used in clinical oncology. It is known that hemin, endogenious compound, has the ability to modulate DOX cytotoxicity. We found that DOX toxicity against mammalian cancer cells can be decreased in vitro in the presence of teraftal (ТF), the component anticancer binaric catalytic system (TF + ascorbic acid).Purpose . To study the influence of TF on anticancer effect of DOX.Materials and methods . The mouse melanoma cell line B16 / F10 and mouse transplanted tumor B16 were used. The TF ability to protect from DOX-induced cell death were measured by MTT-assay, flow сytometry, light microscopy, cytochemical determination of ß-galactosidase expression, radiometric assay and tumor growth inhibition assay in vivo.Results. The sensitivity of mouse melanoma cell line B16 / F10 to DOX decreased in the presence TF (10–20 mkM) in the mean by 4–6 fold. The same mechanism takes part into the decrease of DOX cytotoxicity at the presence of TF / hemin khown which connects with the cell ability to accumulate of drug. TF protect the mouse melanoma cells B16 / F10 from apoptosis, induced by DOX throwing switching on cell premature senescence programme. The antitumor effect of DOX against mouse transplanted melanoma B16 at presence of TF was the same as DOX alone.Conclusions. The TF potency to decrease the sensitivity of cancer cells to DOX in vitro does not correlate with its ability to modulate аnthracycline antibiotics anticancer effect in vivo.