• Corpus ID: 6944436

Reversal of resistance to vincristine in P388 leukemia by various polycyclic clinical drugs, with a special emphasis on quinacrine.

@article{Inaba1988ReversalOR,
  title={Reversal of resistance to vincristine in P388 leukemia by various polycyclic clinical drugs, with a special emphasis on quinacrine.},
  author={Makoto Inaba and E Maruyama},
  journal={Cancer research},
  year={1988},
  volume={48 8},
  pages={
          2064-7
        }
}
We investigated several lipophilic drugs with a polycyclic structure for their effect on the net uptake of vincristine in vincristine-resistant P388 leukemia cells. Fourteen of 23 agents promoted vincristine uptake in the resistant cells. The net increase in vincristine uptake was caused by prevention of its outward transport rather than by stimulation of inward transport. Some of these drugs, e.g., quinacrine, dilazep, syrosingopine, simetride, etc., remarkably potentiated the cytotoxicity of… 

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References

SHOWING 1-10 OF 12 REFERENCES
Non-antitumor vinca alkaloids reverse multidrug resistance in P388 leukemia cells in vitro.
TLDR
Results provide further support for the hypothesis that both anthracyclines and vinca alkaloids can inhibit their own efflux process by interacting with the cell membrane, and this similarity provides a basis for their reciprocal cross-resistance, irrespective of their different chemical structures.
Increased accumulation of vincristine and adriamycin in drug-resistant P388 tumor cells following incubation with calcium antagonists and calmodulin inhibitors.
TLDR
The high intracellular drug accumulation was directly related to the enhancement of the cytotoxicity of the antitumor agents, and the vincristine and Adriamycin resistance in these cells was circumvented.
Lysosomotropic agents reverse multiple drug resistance in human cancer cells.
Anthracycline resistance in P388 murine leukemia and its circumvention by calcium antagonists.
TLDR
An energy-dependent outward transport system in P388/ADR which limits drug accumulation and could not account for the level of daunorubicin resistance observed in the P388 /ADR cell line, nor could resistance be wholly circumvented by calcium antagonists.
Kinetic analysis of active efflux of vincristine from multidrug-resistant P388 leukemia cells.
TLDR
A saturable process of not only influx but also efflux of vincristine was observed for the first time with both parental and multidrug-resistant P388 leukemia cells, suggesting the existence of a carrier-mediated system for influx and efflux.
Overcoming drug resistance in cancer cells with synthetic isoprenoids.
TLDR
In vivo experiments with P388/VCR-bearing mice showed that both SDB-ethylenediamine and verapamil overcame vincristine resistance, but PMB-decaprenylamine showed only slight activity.
Mode of action of calcium antagonists which alter anthracycline resistance.
Circumvention of vincristine and Adriamycin resistance in vitro and in vivo by calcium influx blockers.
TLDR
Calcium influx blockers, which possess coronary vasodilator activity, greatly enhanced the cytotoxicity of vincristine (VCR) in tumor cells and especially in VCR-resistant sublines of P388 leukemia (P388/V CR) and human K562 myelogenous leukemia.
Reversal of multidrug resistance by non-antitumor anthracycline analogs.
It was found that three synthetic anthracycline analogs lacking not only antitumor activity but also calcium-antagonizing action possessed an activity to potentiate vincristine cytotoxicity against
Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukaemia cells.
TLDR
There is no correlation between the ability of these compounds to inhibit calcium uptake in synaptic vesicles and their potency in restoring the sensitivity of P388/ADR cells to doxorubicin.
...
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