A Transition State Analogue of 5′-Methylthioadenosine Phosphorylase Induces Apoptosis in Head and Neck Cancers

    June 2007 in “ Journal of Biological Chemistry ”
    Indranil Basu, Grace Cordovano, Ishita Das, Thomas J. Belbin, Chandan Guha, Vern L. Schramm
    TLDR MT-DADMe-ImmA can selectively kill head and neck cancer cells without harming normal cells.
    The study explored the effects of MT-DADMe-ImmA, an inhibitor of 5′-methylthioadenosine phosphorylase (MTAP), on head and neck cancer cell lines, particularly FaDu and Cal27. The treatment with MT-DADMe-ImmA and 5′-methylthioadenosine (MTA) increased MTA concentrations, decreased polyamines, and induced apoptosis in these cancer cells by causing mitochondrial dysfunction and changes in DNA methylation. The combination treatment was selective for cancer cells, sparing normal fibroblasts and MTAP-deficient breast cancer cells. In a mouse model, MT-DADMe-ImmA led to tumor remission without significant toxicity, suggesting its potential as a selective anticancer agent for tumors sensitive to reduced CpG island methylation.
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