Abstract
Suramin is a poiysulfonated naphthylurea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10”4 and 9 x 10-5 M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin-induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using 125I-IGF-I and found that suramin displaced l25I-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1830-1835 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 52 |
| Issue number | 7 |
| State | Published - 1992 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Suramin Inhibits the Growth of Human Rhabdomyosarcoma by Interrupting the Insulin-like Growth Factor II Autocrine Growth Loop. / Minniti, Caterina P.; Maggi, Mario; Helman, Lee J.
In: Cancer Research, Vol. 52, No. 7, 1992, p. 1830-1835.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suramin Inhibits the Growth of Human Rhabdomyosarcoma by Interrupting the Insulin-like Growth Factor II Autocrine Growth Loop
AU - Minniti, Caterina P.
AU - Maggi, Mario
AU - Helman, Lee J.
PY - 1992
Y1 - 1992
N2 - Suramin is a poiysulfonated naphthylurea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10”4 and 9 x 10-5 M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin-induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using 125I-IGF-I and found that suramin displaced l25I-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach.
AB - Suramin is a poiysulfonated naphthylurea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10”4 and 9 x 10-5 M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin-induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using 125I-IGF-I and found that suramin displaced l25I-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach.
UR - http://www.scopus.com/inward/record.url?scp=0026780214&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026780214&partnerID=8YFLogxK
M3 - Article
VL - 52
SP - 1830
EP - 1835
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -