In vitro effects of pentoxifylline and doxorubicin on cell survival and DNA damage in sensitive and MDR-P388 leukemia cells.
The utility of chemosensitizers to improve efficacy of chemotherapy is now gaining importance. This report investigated whether an active hemorheological agent, pentoxifylline (PTX), can circumvent drug resistance in parental (P388/S) and multidrug resistant (P388/DOX) P388 leukemia cells. For detection of doxorubicin (DOX) resistance and reversal of this resistance by PTX, the incorporation of nucleic acid precursor was measured after addition of DOX and PTX, respectively. The effect of PTX on the induction of DNA strand breaks by DOX was also examined. Increased fragmentation of DNA was illustrated in P388/DOX leukemia cells exposed to the combination of DOX and PTX. The most prominent feature of the multidrug-resistant cell is the reduced accumulation of the drug intracellularly. P388/DOX cells showed less accumulation of DOX in the cell as compared to that of the parental cell line. Further studies demonstrated that PTX significantly enhanced the intracellular accumulation of DOX in both the cell lines. These studies warrant the use of PTX as an adjuvant in cancer chemotherapy.
Viladkar
A
A
Chemotherapy Division, Tata Memorial Centre, Parel, Bombay, India.
Chitnis
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D007941:Leukemia P388 / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D004317:Doxorubicin; D010431:Pentoxifylline