Mechanisms of actio of poly-plat, a novel platinum antineoplastic agent.
Action of Cisplatin (cis-dichlorodiammine platinum II) and Poly-Plat [poly-[(trans-1,2-diaminocyclohexane) pla-tinum]-carboxyamylose] on tumor cells was examined using human fibrosarcoma (HT1080) and Walker rat carcinoma (WRC-256) in culture. These cells were treated with Poly-Plat (10 microg/ml) or Cisplatin (10 mg/ml) for 2-5 days. Peritoneal macrophages were treated with Cisplatin (10 microg/ml) or Poly-Plat (10 microg/ml) for 2 hours and allowed to grow in normal medium for 48 hours. Supernatants from treated macrophages were collected at 0, 4, 12, 24 and 48 hours and IL-2 levels were examined using ELISA technique. The cytotoxicity of these supernatants was examined using HT1080 and WRC-256 cells. Apoptotic assays were used to determine the cytotoxic effects of drugs and macrophage supernatants on tumor cells. These results demonstrate the ability of Poly-Plat to arrest the growth of tumor cells and activate macrophages to induce apoptosis in the cell lines tested.
Telgenhoff
Dale J
DJ
Department of Zoology, Michigan State University, East Lansing 48824, USA.
Aggarwal
Surinder K
SK
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008938:Mitosis / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007376:Interleukin-2; D009944:Organoplatinum Compounds; C111406:poly(trans-1,2-diaminocyclohexane)platinum-carboxyamylose; D002945:Cisplatin