Scavenger-receptor-mediated delivery of daunomycin elicits selective toxicity towards neoplastic cells of macrophage lineage.
Transformed cells of macrophage lineage such as J774A.1, P388D1 and IC21 take up and degrade a conjugate of the antineoplastic drug, daunomycin, with maleylated BSA with high efficiency and saturation kinetics through the scavenger receptors expressed on the surface of these cells. By contrast, transformed cells of non-macrophage lineage, namely L929, EL4, Bowes melanoma and CHO (Chinese-hamster ovary), do not take up and degrade the conjugate, indicating that these cells are scavenger-receptor-deficient. In the conjugated form, about 0.1 microM-daunomycin cause 50% inhibition in the uptake of [3H]thymidine by the receptor-bearing J774A.1 cells, whereas the receptor-deficient Bowes-melanoma cells are not affected. Free daunomycin (0.1 microM) does not significantly affect the uptake of [3H]thymidine by either cell type. Treatment of cells derived from intraperitoneal tumours induced in BALB/C mice by J774A.1 cells with 0.4 microM-daunomycin in the conjugated form for 5 h abolished their ability to form tumours in BALB/C mice. By contrast, transplantation of untreated cells or cells treated with free daunomycin under identical conditions led to tumour formation and subsequent death of the BALB/C mice. These results indicate that this modality for selective elimination of scavenger-receptor-bearing neoplastic cells may be useful for the treatment of histiocytic malignancies in which cells of macrophage lineage turn malignant.
Mukhopadhyay
A
A
Institute of Microbial Technology, Chandigarh, India.
Mukhopadhyay
B
B
Srivastava
R K
RK
Basu
S K
SK
D000418:Albumins / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D003630:Daunorubicin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D007457:Iodine Radioisotopes; D008024:Ligands; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine; D014407:Tumor Cells, Cultured
D000418:Albumins; D007457:Iodine Radioisotopes; D008024:Ligands; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C049877:maleylalbumin; D012710:Serum Albumin, Bovine; D003630:Daunorubicin