Ch3

Squalamine

Squalamine specifically inhibits brush-border Na+/H+ exchanger isoform NHE3, a sodium-hydrogen exchanger present on cell surfaces that regulates intracellular pH, and is also known to regulate endothelial cell volume and shape.36

Cancer cells secrete endothelial cell growth factors that stimulate vascular endothelial cell growth factor receptors (VEGFR), which activates MAP kinase pathways involved in blood vessel growth. Inhibition of the sodium-proton exchanger leads to changes in intracellular pH and subsequent inhibition of MAP kinase activity (Fig. 10.9).37 Squalamine also interacts with calmodulin and possibly with other signaling pathways.

Tumor cell

Endothelial cell growth factors

NHE3 Na+/H+ exchanger

Squalamine

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