Plicamycin Explained

Plicamycin (INN, also known as mithramycin; trade name Mithracin) is an antineoplastic antibiotic produced by Streptomyces plicatus. It is an RNA synthesis inhibitor.[1] The manufacturer discontinued production in 2000. Several different structures are currently reported in different places all with the same chromomycin core, but with different stereochemistry in the glycoside chain, a 1999 study has re-investigated the compound and proposed a revised structure.[2]

Uses

Plicamycin has been used in the treatment of testicular cancer,[3] [4] Paget's disease of bone,[5] [6] and, rarely, the management of hypercalcemia.

Plicamycin has been tested in chronic myeloid leukemia.[7]

Plicamycin is currently used in multiple areas of research, including cancer cell apoptosis[8] and as a metastasis inhibitor.[9]

One elucidated pathway shows it interacts by cross-binding chromatin GC-rich promoter motifs, thereby inhibiting gene transcription.[10]

External links

Notes and References

  1. Web site: Mithramycin A . Fermentek.
  2. Wohlert SE, Künzel E, Machinek R, Méndez C, Salas JA, Rohr J . The structure of mithramycin reinvestigated . Journal of Natural Products . 62 . 1 . 119–121 . January 1999 . 9917296 . 10.1021/np980355k .
  3. Kennedy BJ, Torkelson JL . Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin) . Medical and Pediatric Oncology . 24 . 5 . 327–328 . May 1995 . 7700186 . 10.1002/mpo.2950240511 .
  4. Brown JH, Kennedy BJ . Mithramycin in the Treatment of Disseminated Testicular Neoplasms . The New England Journal of Medicine . 272 . 3 . 111–118 . January 1965 . 14224214 . 10.1056/NEJM196501212720301 .
  5. Hall TJ, Schaeublin M, Chambers TJ . The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro . Biochemical and Biophysical Research Communications . 195 . 3 . 1245–1253 . September 1993 . 8216256 . 10.1006/bbrc.1993.2178 .
  6. Remsing LL, Bahadori HR, Carbone GM, McGuffie EM, Catapano CV, Rohr J . Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target . Biochemistry . 42 . 27 . 8313–8324 . July 2003 . 12846580 . 10.1021/bi034091z .
  7. Dutcher JP, Coletti D, Paietta E, Wiernik PH . A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia . Leukemia Research . 21 . 5 . 375–380 . May 1997 . 9225062 . 10.1016/S0145-2126(96)00108-7 .
  8. Lee TJ, Jung EM, Lee JT, Kim S, Park JW, Choi KS, Kwon TK . Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites . Molecular Cancer Therapeutics . 5 . 11 . 2737–2746 . November 2006 . 17121920 . 10.1158/1535-7163.MCT-06-0426 . free .
  9. Lin RK, Hsu CH, Wang YC . Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells . Anti-Cancer Drugs . 18 . 10 . 1157–1164 . November 2007 . 17893516 . 10.1097/CAD.0b013e3282a215e9 .
  10. Majee S, Chakrabarti A . Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles . Biochemical Pharmacology . 57 . 9 . 981–987 . May 1999 . 10796068 . 10.1016/S0006-2952(98)00374-8 .

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