Specific antioxidant compounds differentially modulate cytotoxic activity of doxorubicin and cisplatin: in vitro and in vivo study

Abstract

AimTo use the antioxidant compounds (sodium selenite, selenomethionine, D-pantethine) for modulation of cytotoxic effect of doxorubicin and cisplatin toward wild type and drug-resistant mutants of several human tumor cells. Similar treatments were applied in vivo toward adult male Wistar rats.MethodsHuman tumor cells of different lines (HCT-116, Jurkat and HL-60) with various mechanisms of drug-resistance were treated with doxorubicin or cisplatin, alone or in combination with sodium selenite, selenomethionine, or D-pantethine. Cell viability, induction of apoptosis, and production of O2- radicals were measured. Activity of redox potential modulating enzymes was measured in the liver and blood plasma of adult male Wistar rats subjected to similar treatments.ResultsAll antioxidants used in physiologically harmless concentration inhibited cytotoxic action of doxorubicin toward tumor cells sensitive to chemotherapy treatment by 15%-30%, and slightly enhanced cytotoxic effect of this medicine toward drug-resistant malignant cells. At the same time, there was no significant effect of these antioxidants on cisplatin action. Such effects were accompanied by a complete inhibition of production of superoxide radicals induced by doxorubicin. The results of in vivo study in adult male Wistar rats were in agreement with the results of in vitro study of human tumor cells.ConclusionProtective effect of specific antioxidant agents during cytotoxic action of doxorubicin was demonstrated in vitro in drug-sensitive human tumor cells and in adult male Wistar rats, while there was no protective effect in drug-resistant sub-lines of these tumor cells during action of doxorubicin and cisplatin.

MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2

“…Chemotherapeutic agents, cisplatin in particular, are widely used in the non-small cell lung cancer treatment. The main mechanism of chemo-drug action is to form intra-and inter-strand with tumor cell DNA and in turn induce tumor apoptosis [19]. However, the resistance to cisplatin represents a significant barrier to improve the longterm overcome of patients with NSCLC [20].…”

Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down‐Regulation of CXCL12‐Induced T Cell Migration

“…Except its metabolic derivatives, pantethine itself exerts specific effects. Apart from its antioxidant properties (Panchuk et al, ), it stimulates lipolysis while it inhibits fatty acid (FA) synthesis (Cighetti et al, ; Bocos and Herrera, ). Moreover, it inhibits HMG‐CoA reductase activity (Cighetti et al, ), the rate‐limiting step of cholesterol synthesis, via a thiol/disulfide exchange reaction (Gilbert and Stewart, ; Cappel and Gilbert, ).…”

Cytotoxic activity of the cluster rhenium compound with ?-alanine ligands

“…Both necrotic and apoptotic pathways of cells death are common for Jurkat cells [11,12,17]. Proapoptotic concentrations of cisplatin (up to 30 μM) induced apoptosis.…”

“…The studied compounds were added at various concentrations noted above. After 72 h of incubation, the alive and dead apoptotic cells were counted according to [11,12]. The viability of cells was assessed by dye exclusion test with 1% trypan blue [11].…”

“…After 72 h of incubation, the alive and dead apoptotic cells were counted according to [11,12]. The viability of cells was assessed by dye exclusion test with 1% trypan blue [11]. LC 50 index was used, calculated as a concentration of drug, which kills 50 % cells in comparison with a control culture by Reed-Muench method [13].…”