Mammalian cardenolides in cancer prevention and therapeutics.

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  • Author(s): Al-Ghoul M;Al-Ghoul M; Valdes R Jr
  • Source:
    Therapeutic drug monitoring [Ther Drug Monit] 2008 Apr; Vol. 30 (2), pp. 234-8.
  • Publication Type:
    Journal Article; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 7909660 Publication Model: Print Cited Medium: Print ISSN: 0163-4356 (Print) Linking ISSN: 01634356 NLM ISO Abbreviation: Ther Drug Monit Subsets: MEDLINE
    • Publication Information:
      Publication: Hagerstown, MD : Lippincott Williams & Wilkins
      Original Publication: [New York] Raven Press.
    • Subject Terms:
      Anticarcinogenic Agents*/metabolism ; Anticarcinogenic Agents*/pharmacology ; Cardenolides*/metabolism ; Cardenolides*/pharmacology ; Saponins*/metabolism ; Saponins*/pharmacology; Neoplasms/*prevention & control; Adrenal Glands/metabolism ; Animals ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Digoxin/analogs & derivatives ; Digoxin/metabolism ; Digoxin/pharmacology ; Digoxin/therapeutic use ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Ouabain/analogs & derivatives ; Ouabain/metabolism ; Ouabain/pharmacology ; Ouabain/therapeutic use
    • Abstract:
      Digoxin-like immunoreactive factor (DLIF) and ouabain-like factor (OLF) are the mammalian counterparts to the plant-derived cardiotonic steroids digoxin and ouabain. Compelling evidence indicates that the cardiotonic steroids may have anticancer properties. Recent evidence indicates that low (nanomolar) concentrations of DLIF selectively induce cell death in transformed cells, while sparing normal cells, and is even more potent than the plant-derived compounds. The discovery that these endogenous molecules may play a role in the regulation of cancer cell proliferation provides a potentially new paradigm for the physiologic role of DLIF and OLF. In addition, the possible use of digoxin itself as a therapeutic agent in cancer has been explored, and evidence suggests that its conversion to dihydrodigoxin may be involved in regulating anticancer activity. The mechanism(s) for the pro-apoptotic property of these compounds is not known. In this brief review, we will discuss the proposed mechanism of action of digoxin, ouabain, DLIF, and OLF as anticancer compounds and discuss the effects that metabolic conversion to their dihydro-derivatives may have on this activity. From the perspective of therapeutic drug monitoring, these findings suggest some potential new challenges in the need to measure concentrations of digoxin and dihydrodigoxin as well as their endogenous counterparts DLIF and OLF in serum.
    • Number of References:
      40
    • Accession Number:
      0 (Anticarcinogenic Agents)
      0 (Cardenolides)
      0 (Saponins)
      0 (digoxin-like factors)
      1183-35-3 (dihydroouabain)
      5297-10-9 (dihydrodigoxin)
      5ACL011P69 (Ouabain)
      73K4184T59 (Digoxin)
    • Publication Date:
      Date Created: 20080328 Date Completed: 20080711 Latest Revision: 20131121
    • Publication Date:
      20231215
    • Accession Number:
      10.1097/FTD.0b013e31816b90ff
    • Accession Number:
      18367987