Hkih-affinity interaction of hydrophobic peptidh derivatives with the human multjdrlki rksistancf. protein, mdri

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Abstract

The function of the multidrug resistance protein (MDRI) is one of the major causes of multiple chemotherapy resistance in tumor cells. We have developed a group of hydrophohic peptide-based molecules with original structures (REVERSINs), which act as high-affinity ligands of the MDRI protein. In this study we have examined the effects of REVERSINs on the vanadate-sensitive MDRI-ATPase activity in isolated cell membranes, on the M DR I-dependent Calcein AM extrusion, and on the modulation ot cytotoxicity of vincristine and adriamycin in MDRI-expressing tumor cells. We found that RKVERSINs significantly stimulated MDRI-ATPase activity, while inhibited fluorescent dye extrusion in the low micromolar concentrations. In these latter concentrations RKVERSINs also inhibited M DR I-dependent tumor cell resistance against vincristine and adriamycin, while had no toxic effect on the control cells. We suggest that REVERSINs are good candidates for the development of specific agents to prevent multidrug resistance in cancer.

Original languageEnglish
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - 1997

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P-Glycoproteins
multiple drug resistance
hydrophobic bonding
Hydrophobic and Hydrophilic Interactions
Derivatives
Tumors
Cells
vincristine
Vincristine
Proteins
doxorubicin
proteins
Doxorubicin
Extrusion
Adenosine Triphosphatases
Neoplasms
extrusion
adenosinetriphosphatase
Chemotherapy
Vanadates

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

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title = "Hkih-affinity interaction of hydrophobic peptidh derivatives with the human multjdrlki rksistancf. protein, mdri",
abstract = "The function of the multidrug resistance protein (MDRI) is one of the major causes of multiple chemotherapy resistance in tumor cells. We have developed a group of hydrophohic peptide-based molecules with original structures (REVERSINs), which act as high-affinity ligands of the MDRI protein. In this study we have examined the effects of REVERSINs on the vanadate-sensitive MDRI-ATPase activity in isolated cell membranes, on the M DR I-dependent Calcein AM extrusion, and on the modulation ot cytotoxicity of vincristine and adriamycin in MDRI-expressing tumor cells. We found that RKVERSINs significantly stimulated MDRI-ATPase activity, while inhibited fluorescent dye extrusion in the low micromolar concentrations. In these latter concentrations RKVERSINs also inhibited M DR I-dependent tumor cell resistance against vincristine and adriamycin, while had no toxic effect on the control cells. We suggest that REVERSINs are good candidates for the development of specific agents to prevent multidrug resistance in cancer.",
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N2 - The function of the multidrug resistance protein (MDRI) is one of the major causes of multiple chemotherapy resistance in tumor cells. We have developed a group of hydrophohic peptide-based molecules with original structures (REVERSINs), which act as high-affinity ligands of the MDRI protein. In this study we have examined the effects of REVERSINs on the vanadate-sensitive MDRI-ATPase activity in isolated cell membranes, on the M DR I-dependent Calcein AM extrusion, and on the modulation ot cytotoxicity of vincristine and adriamycin in MDRI-expressing tumor cells. We found that RKVERSINs significantly stimulated MDRI-ATPase activity, while inhibited fluorescent dye extrusion in the low micromolar concentrations. In these latter concentrations RKVERSINs also inhibited M DR I-dependent tumor cell resistance against vincristine and adriamycin, while had no toxic effect on the control cells. We suggest that REVERSINs are good candidates for the development of specific agents to prevent multidrug resistance in cancer.

AB - The function of the multidrug resistance protein (MDRI) is one of the major causes of multiple chemotherapy resistance in tumor cells. We have developed a group of hydrophohic peptide-based molecules with original structures (REVERSINs), which act as high-affinity ligands of the MDRI protein. In this study we have examined the effects of REVERSINs on the vanadate-sensitive MDRI-ATPase activity in isolated cell membranes, on the M DR I-dependent Calcein AM extrusion, and on the modulation ot cytotoxicity of vincristine and adriamycin in MDRI-expressing tumor cells. We found that RKVERSINs significantly stimulated MDRI-ATPase activity, while inhibited fluorescent dye extrusion in the low micromolar concentrations. In these latter concentrations RKVERSINs also inhibited M DR I-dependent tumor cell resistance against vincristine and adriamycin, while had no toxic effect on the control cells. We suggest that REVERSINs are good candidates for the development of specific agents to prevent multidrug resistance in cancer.

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