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 MLT 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. MLT exerted no clear-cut effects on the HEp-2 cell line. In contrast, DOX at concentrations of 0.1 and 1.0 microg/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.
Fic
Magdalena
M
Department of Histology and Embryology, University School of Medicine, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland. fima@ak.am.wroc.pl
Podhorska-Okolow
Marzena
M
Dziegiel
Piotr
P
Gebarowska
Elzbieta
E
Wysocka
Teresa
T
Drag-Zalesinska
Malgorzata
M
Zabel
Maciej
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008550:Melatonin / Q000494:pharmacology*; D009336:Necrosis; D012142:Respiratory Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D000975:Antioxidants; D004338:Drug Combinations; D004317:Doxorubicin; D008550:Melatonin