Showing papers by "Ivanka Markovic published in 2006"
TL;DR: Gene expression data confirmed the induction of mdr1 (P-gp), as judged by the observed 15-fold increase in its mRNA concentration in doxorubicin-resistant NCI-H460/R cells, which should develop a rationale for a novel treatment of NSCLC with appropriate modulators of resistance aimed at improving the outcome of the acquired drug resistance.
Abstract: Exposure of human non-small cell lung cancer cells (NCI-H460) to gradually increasing concentrations of doxorubicin resulted in the appearance of a new cell line (NCI-H460/R) that was resistant to doxorubicin (96.2-fold) and cross-resistant to etoposide, paclitaxel, vinblastine and epirubicin. Slight cross-resistance to two MDR-unrelated drugs 8-Cl-cAMP and sulfinosine was observed. Flow cytometry analysis showed that the accumulation of doxorubicin in the resistant cells was 88.4% lower than in the parental cells. Also, verapamil significantly decreased the efflux rate in NCI-H460 and NCI-H460/R cells, whereas curcumin inhibited the efflux in NCI-H460 cells only. Gene expression data confirmed the induction of mdr1 (P-gp), as judged by the observed 15-fold increase in its mRNA concentration in doxorubicin-resistant NCI-H460/R cells. In contrast, mrp1 and lrp expression was unaffected by the doxorubicin resistance. Further work should develop a rationale for a novel treatment of NSCLC with appropriate modulators of resistance aimed at improving the outcome of the acquired drug resistance.
88 citations
TL;DR: Results indicate that apoptosis was the predominant type of cell death after treatment of SK-N-SH cells with both substances, as well as with their combinations.
Abstract: To identify purine analogs that could be effective in treating neuroblastomas, we tested the anticancer properties of sulfinosine, 8-Cl-cAMP and 8-Cl-adenosine in the SK-N-SH cell line. First we examined the effects of these three agents on cell growth inhibition and cell viability by the BrdU and Sulforhodamine B assay. Treatment of SK-N-SH cells with increasing concentrations of these compounds led to a significant inhibition of cell proliferation and decrease of cell viability in a time- and dose-dependant manner at micromolar concentration (<10 μM). Treatment with a combination of sulfinosine and 8-Cl-cAMP resulted in synergistic effects on growth inhibition, cell cycle arrest and induction of apoptosis. Flow-cytometric analysis showed that 8-Cl-cAMP arrested the cells in the G0/G1 phase and sulfinosine blocked cell cycle progression at the G2/M stage, in contrast to the combined effects of both agents that did not arrest growth at any particular phase of the cell cycle. Further analysis of apoptosis induction demonstrated an increase from 17 to 24% of both early and late apoptotic cells and a very low percentage of necrotic cells. These results indicate that apoptosis was the predominant type of cell death after treatment of SK-N-SH cells with both substances, as well as with their combinations.
10 citations