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Suramin inhibits growth of human osteosarcoma xenografts in nude mice
1Department of Cell Biology, Faculty of Health Sciences, University of Linköping, Sweden.
Abstract:
The effect of suramin on tumor growth and morphology in two different human osteosarcoma xenografts (L-I OSM and L-II OSM) grown in BALB/cA-nu/nu mice was studied. Suramin (total dose, 720 mg/kg) given by i.p. injection (60 mg/kg/dose) for up to 9 weeks significantly inhibited osteosarcoma cell growth in both tumors, suramin-treated tumors showing only one-third or less of the volume of nontreated controls. Cell cycle distribution of tumor cells measured by DNA flow cytometry demonstrated that suramin treated caused accumulation of cells in the S and G2 phases of the cell cycle, in both L-I OSM and L-II OSM. In the aneuploid L-II OSM tumor suramin preferentially inhibited the growth of aneuploid cells, leading to a decrease in the ratio of aneuploid to diploid cells. Both osteosarcomas retained their histological appearance and the liver, spleen, heart, and kidneys of the treated animals were unaffected by suramin. These results are compatible with the view that suramin inhibits the growth of human osteosarcomas by cytostatic effects.
Insights
Suramin significantly inhibited human osteosarcoma growth in mice by causing cell cycle arrest. This cancer drug demonstrated cytostatic effects without harming major organs in treated animals.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Osteosarcoma is a primary bone cancer with limited treatment options.
- Understanding novel therapeutic agents for osteosarcoma is crucial.
Purpose of the Study:
- To investigate the anti-tumor effects of suramin on human osteosarcoma xenografts.
- To determine the impact of suramin on tumor cell cycle and histology.
Main Methods:
- Two human osteosarcoma xenografts (L-I OSM and L-II OSM) were grown in immunodeficient mice.
- Suramin was administered via intraperitoneal injection over a 9-week period.
- Tumor volume, cell cycle distribution (DNA flow cytometry), and histology were analyzed.
Main Results:
- Suramin significantly inhibited tumor growth, reducing tumor volume by at least two-thirds.
- Suramin induced cell cycle arrest in the S and G2 phases for both osteosarcoma models.
- Suramin preferentially inhibited aneuploid cell growth in the L-II OSM model.
- Histological analysis showed no adverse effects on major organs (liver, spleen, heart, kidneys).
Conclusions:
- Suramin exhibits significant cytostatic effects against human osteosarcoma xenografts.
- Suramin's mechanism involves cell cycle arrest and preferential inhibition of aneuploid cells.
- Suramin is a potential therapeutic agent for osteosarcoma with a favorable safety profile in preclinical models.
