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Biomedical subjects

A Krishan

Publications and source records attributed to A Krishan.

113 records · Page 7Linked to original sources
PubMedDate not supplied

Effect of taxol on vinblastine sulfate-induced crystallization of tubulin.

In human lung adenocarcinoma cells exposed to vinblastine (VLB) and stained with fast green, large tubulin crystals were seen in the cytoplasm. In contrast cells exposed to taxol had prominent bundles of stabilized microtubules. Pre- or co-incubation of cells with taxol before exposure to VLB prevented formation of the crystals. However, VLB did not prevent formation of stabilized microtubules by taxol if added at the same time. Under a fluorescent microscope, VLB induced crystals stained with secondary antibodies against anti-alpha- and anti-beta- tubulin antibodies. Neither of the drugs altered binding of the antibodies to these crystals.

Adenocarcinoma↗
PubMedDate not supplied

Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic P388 and P388/R84 cells.

The induction of apoptosis by doxorubicin (DOX) alone or in the presence of efflux blockers, verapamil (VPL) or trifluoperazine (TFP), and of bcl-2 and mdr-1 gene expression was analyzed in murine leukemic P388 and doxorubicin resistant P388/R84 cells. Incubation with DOX (0.1-1 microM) for 24 hours induced apoptosis in sensitive cells but not in the resistant P388/R84 cells. Flow cytometric analysis of apoptosis by terminal dideoxynucleotidyl (TdT) assay showed that 1 microM DOX induced apoptosis in 70% of P388 cells and in less than 5% of P388/R84 cells. When P388/R84 resistant cells were co-incubated with DOX and efflux blockers (10 microM VPL or 15 microM TFP), enhanced cellular DOX accumulation was accompanied by apoptosis. Quantitative analysis of DNA fragmentation by 14C-thymidine incorporation and gel electrophoresis of fragmented DNA confirmed the results from TdT assay and showed enhancement of DOX-induced DNA fragmentation in the presence of efflux blockers (VPL or TFP). DOX + VPL and DOX + TFP combination treatments induced apoptosis in upto 55% and 83% of P388/R84 cells, respectively. mdr-1 mRNA and P-gp expression were not altered during DOX-induced apoptosis. The results suggest that in murine leukemic cells, down-regulation of bcl-2 mRNA expression occurs during DOX-induced apoptosis and it depends on the cellular drug retention determined by mdr-1/P-gp drug efflux.

Animals↗