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  • Title: Levistolide A overcomes P-glycoprotein-mediated drug resistance in human breast carcinoma cells.
    Author: Chen F, Wang T, Wang J, Wang ZQ, Qian M.
    Journal: Acta Pharmacol Sin; 2008 Apr; 29(4):458-64. PubMed ID: 18358092.
    Abstract:
    AIM: The aim of the present study was to investigate the reversing effect of levistolide A (LA) on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in human breast carcinoma Bcap37/MDR1 cells. METHODS: After chemotherapeutic drugs (adriamycin or vincristine) used alone or in combination with LA, cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and cell cycle distribution by flow cytometry. RT-PCR was used to detect MDR1 gene transcription and the Western blot assay was used to assess P-gp expression and the cleavages of poly(ADP-ribose) polymerase and caspase-3. Apoptosis was detected by terminal transferase-mediated dUTP nick end-labeling assay. Moreover, the P-gp function was evaluated by the intracellular accumulation of the P-gp substrate detected by flow cytometry. RESULTS: We found the subcytotoxic doses of LA significantly enhanced adriamycin- or vincristine- induced G2/M arrest and apoptosis. These effects were consistent with the ability of LA to inhibit P-gp function. Moreover, LA dramatically enhanced the verapamil (VER) ability to reverse drug resistance. CONCLUSION: LA has the potential to be developed as a novel P-gp modulator. Furthermore, the combination of LA and VER might represent a more sufficient but less toxic anti-MDR regimen.
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