Cancer science
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Comparative Study
Adaphostin has significant and selective activity against chronic and acute myeloid leukemia cells.
Adaphostin is a tyrphostin that was designed to inhibit Bcr/Abl tyrosine kinase by altering the binding site of peptide substrates rather than that of adenosine triphosphate, a known mechanism of imatinib mesylate (IM). However, it has been shown that adaphostin-mediated cytotoxicity is dependent on oxidant production and does not require Bcr/Abl. We have tested adaphostin against both Philadelphia chromosome (Ph)-positive (K562, KBM5, KBM5-R [IM resistant KBM5], KBM7, and KBM7-R [IM-resistant KBM7]) and Ph-negative (OCI/AML2 and OCI/AML3) cells, and against cells from patients with chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). ⋯ Adaphostin selectively inhibited colony growth of cells from CML (IM-sensitive and IM-resistant) and AML patients. Analysis of tyrosine phosphorylated proteins after treatment with adaphostin revealed alternate effects in different cells consistent with the modulation of multiple targets. In conclusion, adaphostin showed significant and selective activity against CML and AML cells and its development for clinical testing is warranted.