Cancer mithramycin

The mechanism of action of mithramycin (Mithracin) is similar to that of dactinomycin. It is used in patients with advanced disseminated tumors of the testis and for the treatment of hypercalcemia associated with cancer. Mithramycin may cause gastrointestinal injury, bone marrow depression, hepatic and renal damage, and hemorrhagic tendency (see Chapter 62). 

Since the second complex contains two molecules of drug, therefore, we refer to it as dimer complex. Keeping in view the milli molar concentration of the metal ion present in the cell, possibility of the formation of dimer complex is more under in vivo conditions. However, in certain cases of cancer the metal ion concentration goes down to micro molar range. Under these unusual conditions, complex I is formed. Recently we have shown that mithramycin forms only dimer complex with Zn +, another metal ion playing an important role as cofactor in many enzymes and DNA binding proteins like transcription factors. 

Fitzgerald DJ, Anderson JN (1999) Selective nucleosome disruption by drugs that bind in the minor groove of DNA. J Biol Chem 274(38) 27128-27138 Fox KR, Cons BM (1993) Interaction of mithramycin with DNA fragments complexed with nucleosome core particles comparison with distamycin and echinomycin. Biochemistry. 32(28) 7162—7171 Friedman HS, Kerby T, Calvert, H (2000) Temozolomide and treatment of malignant gliomas. CUn Cancer Res 6 2585-2597... 

Synder RC, Ray R, Blume S, Miller DM (1991) Mithramycin blocks transcriptional initiation of the c-myc PI and P2 promoters. Biochemistry 30 4290-4297 Szyf M (2003) DNA methylation and cancer therapy. Drug Resist Updat 6(6) 341—353 Szyf M, Pakneshan P, Rabbani SA (2004) DNA demethylation and cancer therapeutic implications. 

Lin, R.K., Hsu, C.H. and Wang, YC. (2007) Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells. Anti-Cancer Drugs, 18, 1157-1164. 

Members of this group feature tricyclic carbon framework decorated with two oligosaccharide chains. Mithramycin 48 and chromomycin A3 49 are two aureolic acids that have found their use in cancer chemotherapy. These compounds, interacting with Mg2+, bind GC-rich DNA in a nonintercalative way, and sugar chains are indispensable in stabilizing metal-antibiotic complexes. Carbohydrates are... 

Mithramycin (47) is an antitumor antibiotic isolated from Strep-tomyces plicatus. It currently is used to a limited extent for the treatment of embryonal cell carcinoma of the testes and of cancer-related hypercalcemia (85). It is reported to be a specific inhibitor of the Spl transcription factor in hematopoietic cells (86). 

Mithramycin ) is an (anthracycline group) antibiotic isolated from Streptomyces sp. It has cytotoxic properties and clinically may be used as an oral and parenteral anticancer agent, particularly for testicular cancer, plomestane (inn, usan] (MDL 18962) is a steroid with AROMATASE inhibitor (oestrogen synthetase inhibitor) activity. It is under investigation for some anticancer applications, e.g. for treatment of breast cancer. 

K Fujiwara, et al. Enzyme immunoassay for the quantification of mithramycin using beta-deuterium-galactosidase as a label. Cancer Res 46 1084, 1986. 

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