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Description

A cell-permeable symmetrical cystamine compound that selectively suppresses cellular HIF-1alpha, but not HIF-1beta, protein synthesis without affecting the transcription of HIF-1alpha mRNA or the stability of HIF-1alpha protein. Reduction of cellular HIF-1alpha by KC7F2 treatment (IC50<20 µ,M in LN229 cultures under hypoxia condition) is shown to result in decreased transcriptions of HIF-1alpha-dependent genes, such as CA IX, endothelin 1, enolase 1, and MMP-2. Inhibition of 4EBP1 and S6K phosphorylation, important event for the initiation of protein translation, is also observed in KC7F2 and U87MGD cultures following KC7F2 treatment under hypoxia condition, which may account for, at least in part, the downregulated HIF-1alpha synthesis.