Suramin, an anti‐cancer drug, inhibits protein kinase C and induces differentiation in neuroblastoma cell clone NB2A

Abstract

Protein kinase C purified from rat brain was found to be inhibited by suramin, a substance used originally in the therapy of antitrypanosomic infections and more recently proposed as antineoplastic agent. The inhibition of suramin was competitive with one of the substrates of the enzyme, ATP with a K, of 10 PM. At concentrations adequate to inhibit the isolated enzyme, suramin was shown to slow the rate of proliferation of neuroblastoma NB2A cells in vitro and to induce their differentiation as evidenced by typical morphological changes.

A structure-activity analysis of antagonism of the growth factor and angiogenic activity of basic fibroblast growth factor by suramin and related polyanions

“…These include, in the context of antiproliferation, inhibition of key enzymes involved in the intracellular transduction of mitogenic signals, e.g. phosphoinositol and diacylglycerol kinases (Kopp & Pfeiffer, 1990), protein kinase C (Hensey et al, 1989), DNA polymerases (Spigelman et al, 1987) and topoisomerase II (Bojanowski et al, 1992). Suramin has also been shown to disrupt the coupling of G-proteins to receptors (Butler et al, 1988).…”

Involvement of α‐ and β‐PKC in the differentiation of 3T3‐L1 cells

“…Staurosporine, though first reported to be the most potent inhibitor of PKC [7], was also found to inhibit various protein kinases at a certain range of concentrations [17] and induce cell differentiation in some types of cells [18][19][20]. The concentration of staurosporine used in the present study seems to be suitable for the potentiation of PKC to differentiate the 3T3-LI cells [7,21].…”

“…The present study suggested that inhibition rather than activation of PKC appears to be associated with differentiation of 3T3-L1 cells. There are also some reports that other PKC inhibitors enhanced differentiation in neuroblastoma cells [18,19] and HL-60 cells [20].…”

Molecular modeling of G-protein coupled receptor kinase 2: Docking and biochemical evaluation of inhibitors

“…To extend our study to structurally distinct potential kinase inhibitors not contained in the Fine Chemicals Directory used, we tested suramin, a compound previously shown to inhibit protein kinase C 39 and, very weakly, cAPK 40 . Suramin was docked into the GRK2 model and attained a high GRK2 score with a favorable fit into the central cleft ( Figure 2C [static image]), in preference to cAPK.…”