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Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients.

Authors
  • López-Lázaro, Miguel1
  • Pastor, Nuria
  • Azrak, Sami S
  • Ayuso, María Jesús
  • Austin, Caroline A
  • Cortés, Felipe
  • 1 Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41011, Seville, Spain. [email protected] , (Spain)
Type
Published Article
Journal
Journal of natural products
Publication Date
Nov 01, 2005
Volume
68
Issue
11
Pages
1642–1645
Identifiers
PMID: 16309315
Source
Medline
License
Unknown

Abstract

The cardiac glycosides digitoxin (1) and digoxin (3) have been used in cardiac diseases for many years. During this time several reports have suggested the possible use of digitalis in medical oncology. Several analogues of digitoxin (1) were evaluated for growth inhibition activity in three human cancer cell lines; this study showed that digitoxin (1) was the most active compound and revealed some structural features that may play a role in the growth inhibition activity of these drugs. The IC50 values for 1 (3-33 nM) were within or below the concentration range seen in the plasma of patients with cardiac disease receiving this glycoside (20-33 nM). A renal adenocarcinoma cancer cell line (TK-10) was hypersensitive to this drug, and digitoxin toxicity on these cells was mediated by apoptosis. In vitro experiments showed that 1 at 30 nM induced levels of DNA-topoisomerase II cleavable complexes similar to etoposide, a topoisomerase II poison widely used in cancer chemotherapy. Using the individual cell assay TARDIS, cells exposed to 1 for 30 min showed low but statistically significant levels of DNA-topoisomerase II cleavable complexes; however these complexes disappeared after 24 h exposure.

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