Difference in effects of alkyl-lysophospholipids and verapamil on vincristine transport in vincristine-sensitive and -resistant human myelogenous leukemia K562.
Several kinds of alkyl-lysophospholipids enhanced the accumulation of vincristine (VCR) in both drug-sensitive and -resistant K562 cells. The drugs also augmented the efflux of VCR from the tumor cells. It is assumed that alkyl-lysophospholipids made tumor cells permeable to both the influx and efflux of VCR. The alkyl-lysophospholipids produced nonspecific effects of almost equal intensity in both sensitive and resistant tumor cells. These effects were compared with those of verapamil, a calcium channel blocker. Verapamil, as reported previously, specifically inhibited the efflux of drugs from tumor cells, especially drug-resistant tumor cells, thereby enhancing the accumulation of antitumor agents in the cells. Thus the actions of alkyl-lysophospholipids and verapamil in tumor cells were obviously different. Furthermore, the combined effects of alkyl-lysophospholipids and verapamil were additive or synergistic, indicating that their sites of action may be different.
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D002460:Cell Line; D004351:Drug Resistance; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008246:Lysophospholipids; D010743:Phospholipids / Q000494:pharmacology*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*; D014750:Vincristine / Q000378:metabolism*
D008246:Lysophospholipids; D010743:Phospholipids; D014750:Vincristine; D014700:Verapamil