Immobilized doxorubicin increases the complement susceptibility of human melanoma cells by protecting complement component C3b against inactivation.
Human melanoma cells resistant to killing by monoclonal antibody R24 plus human complement became susceptible after treatment with doxorubicin (adriamycin). Treatment with doxorubicin prevented the rapid degradation of surface-bound complement component C3b that has been identified as a protective mechanism of complement-resistant melanoma cells. Doxorubicin caused the increased complement susceptibility as free drug and after immobilization onto glass beads to prevent cellular uptake. Immobilized doxorubicin was more effective than free drug, causing enhanced complement susceptibility at concentrations where the free drug was no longer active. In contrast to free doxorubicin, which exhibited a direct cytotoxic effect leading to cell death within 4 days, immobilized doxorubicin did not affect cell viability. These findings suggest that combination therapy of the complement-activating monoclonal antibody R24 with the complement-enhancing drug doxorubicin may be a promising approach for the treatment of melanoma.
Panneerselvam
M
M
Bredehorst
R
R
Vogel
C W
CW
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D002460:Cell Line; D003131:Combined Modality Therapy; D003167:Complement Activation; D003179:Complement C3b / Q000276:immunology* / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000628:therapy*; D012995:Solubility
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D005732:Gangliosides; C026226:ganglioside, GD3; D004317:Doxorubicin; D003179:Complement C3b