Potentiation of doxorubicin-induced apoptosis and differentiation by indomethacin in K-562 leukemia cells.
In this study we have examined the antitumor effect of combined administrations of indomethacin (IND) with doxorubicin (DOX) on growth of K-562 leukemia cells. Although, as single drug treatment, only high concentrations of IND reduced growth (>200 microM) and induced apoptosis (>800 microM) of the K-562 cells, a synergistic effects on DOX-induced cell growth inhibition, apoptosis and differentiation were observed during the co-administration of DOX with 10 microM IND. Cells treated with this combination had elevated GSHt level compare to DOX-treated cells. Modulation of GSHt level of DOX-treated cells with Cd2+ ions or BSO confirmed its important role in processes of DOX-induced differentiation. Results of this study showed that IND has a positive effect on therapeutic efficacy of DOX, and could be a perspective modulator in cancer chemotherapy.
Cipák
L
L
Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic.
Paulíková
H
H
Novotný
L
L
Jarosová
M
M
Rauko
P
P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D007213:Indomethacin