Combined effect of lipoic acid and doxorubicin in murine leukemia.
Our experiments indicate that administration of a toxic drug with high rate of free-radical formation (doxorubicin, DOX) combined with an antioxidant (alpha-lipoic acid, LA) may lead to a decrease in drug-toxicity. However, the effects of antioxidant may be concentration-dependent and it is therefore crucial to choose its appropriate dosage. LA at a low concentration (1 micromol/l) acts as a growth factor and at a higher concentration (100 micromol/l) acts as an antiproliferation agent. Both concentrations of LA in combination with DOX were examined in cytotoxic and antitumor effects in L1210 mouse leukemia cells employing a MTT chemosensitivity assay. In most concentration combinations, DOX and LA effect were antagonistic and synergistic action was only found at the higher concentration of both agents (DOX 2.5 micromol/l and LA 100 micromol/l). Use of LA in doxorubicin therapy lead to an increase (though marginally significant) in survival of animals. Combined single-dose administration of DOX (5 mg/kg) and LA (16 mg/kg) lead to super-additive effect of the combination on survival of leukemic mice.
Dovinová
I
I
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Novotný
L
L
Rauko
P
P
Kvasnicka
P
P
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use* / Q000633:toxicity; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008063:Thioctic Acid / Q000627:therapeutic use* / Q000633:toxicity
D008063:Thioctic Acid; D004317:Doxorubicin