M. Abdelfattah, J. Rohr
Aug 25, 2006
Citations
2
Influential Citations
20
Citations
Journal
Angewandte Chemie
Abstract
Mithramycin (1, MTM, Scheme 1, also known as mithramycin A, mithracin, and plicamycin) is an aureolic acid anti-cancer agent produced by various soil bacteria of the genus Streptomyces, including Streptomyces argillaceus (ATCC12956). It inhibits the growth of cancer cells by cross-linking GC-rich DNA, thereby shutting down specificity protein (Sp1 or Sp3) dependent pathways towards proto-oncogenes, such as c-myc,[1] APC,[2] and c-src.[3] The last gene is also associated with the unique hypocalcemic activity of mithramycin.[3] MTM has become a popular biochemical tool to study Sp-dependent signal-transduction pathways, but because of its toxic side effects is rarely used as an anticancer agent, except for the treatment of tumor hypercalcemia refactory to other chemotherapy.[4–8] However, MTM was recently identified as a potential lead drug against neurological diseases,[9,10] arthritis,[11] and for the treatment of hematologic disorders.[12] All these new applications require only very small, less-toxic concentrations of the drug, although the mode-of-action in these contexts remains obscure.