Effect of melatonin on cytotoxicity of doxorubicin toward selected cell lines (human keratinocytes, lung cancer cell line A-549, laryngeal cancer cell line HEp-2)

The pineal hormone melatonin (MLT) has been recognised as a substance capable of alleviating in vivo nephro-, cardio- and myelotoxicity of doxorubicin (DOX) and of other anthracyclines in animal models. However, few data are available on the effects of MLT on cytotoxicity of antineoplastic drugs toward tumor cells in vitro. The present study aimed at the evaluation of effects of ML T and of DOX on selected cell lines. The experiments were conducted on human keratinocytes (primary culture), non-small cell lung cancer (A-549) and laryngeal cancer cell lines (HEp-2). In keratinocytes and in A-549 cells, MLT used at pharmacological concentrations (0. 1 and 1.0 mM) was observed to intensify apoptotic lesions. ML T exerted no clear-cut eftects on the HEp-2 cell line. In contrast, DOX at concentrations of 0.1 and 1.0,mu g/ml intensified apoptosis and augmented the frequency of necrotic lesions in cell nuclei in all the examined cell lines. MLT intensified cytotoxicity of DOX in all cell lines, significantly decreasing cell numbers and promoting apoptosis. The effect was MLT concentration-dependent. MLT decreased the proportion of cells with necrotic lesions.