Transferrin-adriamycin conjugates which inhibit tumor cell proliferation without interaction with DNA inhibit plasma membrane oxidoreductase and proton release in K562 cells.
Conjugates of adriamycin crosslinked to transferrin with glutaraldehyde inhibit proliferation of transformed cells. Conjugates of this type inhibit oxidoreductase activity in the plasma membrane of K562 cells, and the inhibition of electron transport is found at concentrations ten times lower than concentrations of free adriamycin which inhibit electron transport and cell growth. The transferrin-adriamycin conjugate inhibits ferricyanide reduction, diferric transferrin reduction and plasma membrane NADH oxidase activity stimulated by transferrin. Activation of proton release from the K562 cells by diferric transferrin also is inhibited by the conjugate, and conjugate kills cells more effectively than free adriamycin. Since the conjugate does not transfer adriamycin to the nucleus, the growth control may be based on inhibition of the transferrin regulated redox system and Na+/H+ antiport activity at the plasma membrane.
Faulk
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WP
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202.
Barabas
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K
Sun
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IL
Crane
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FL
D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D004579:Electron Transport / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D011522:Protons; D011990:Receptors, Transferrin / Q000187:drug effects*; D017923:Sodium-Hydrogen Exchangers; D014168:Transferrin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
D002352:Carrier Proteins; D004337:Drug Carriers; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011522:Protons; D011990:Receptors, Transferrin; D017923:Sodium-Hydrogen Exchangers; D014168:Transferrin; C028283:diferric transferrin; D004317:Doxorubicin; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases