Steroid hormones inhibit binding of Vinca alkaloid to multidrug resistance related P-glycoprotein.
Multidrug-resistant cells are characterized by the presence of P-glycoprotein on the plasma membrane, which binds and probably transports antitumor agents outside the cells. P-glycoprotein is also present in various normal tissues such as the adrenal gland. To investigate the physiological function of P-glycoprotein, we examined possible endogenous materials which inhibit the binding of vincristine to the resistant cell membrane. The binding was inhibited by steroid hormones, most efficiently by progesterone. Progesterone also reduced the photoaffinity labeling of P-glycoprotein by a photoactive analogue of vindesine. These results suggest that P-glycoprotein in the adrenal gland could have a role in the secretion of steroid hormones.
Naito
M
M
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Yusa
K
K
Tsuruo
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000345:Affinity Labels; D000728:Androgens / Q000494:pharmacology; D001386:Azides; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004351:Drug Resistance; D004967:Estrogens / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D007163:Immunosorbent Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010777:Photochemistry; D011374:Progesterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism*; D014751:Vindesine / Q000031:analogs & derivatives
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000305:Adrenal Cortex Hormones; D000345:Affinity Labels; D000728:Androgens; D001386:Azides; D004967:Estrogens; D006728:Hormones; D008562:Membrane Glycoproteins; C048694:N-(4-azidobenzoyl)-N'-beta-aminoethylvindesine; D011374:Progesterone; D014750:Vincristine; D000255:Adenosine Triphosphate; D014751:Vindesine