Cart
Article
Digitoxin Inhibits the Growth of Cancer Cell Lines at Concentrations Commonly Found in Cardiac Patients
Full Text HTML
Hi-Res PDFPurchase the full-text
- PDF/HTML,
figures/images,
references and tables,
(where available)
Section: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.
Citing Articles
Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 9 ACS Journal articles (5 most recent appear below).
Cytotoxic Cardiac Glycosides and Other Compounds from Asclepias syriaca
Juan J. Araya, Kelly Kindscher, and Barbara N. TimmermannJournal of Natural Products2012 75 (3), 400-407Cytotoxic Cardiac Glycosides and Other Compounds from Asclepias syriaca
Juan J. Araya, Kelly Kindscher, and Barbara N. TimmermannJournal of Natural Products2012 75 (3), 400-407Phytochemical investigation of the dried biomass of Asclepias syriaca afforded five new compounds (1–5), along with 19 known structures. Overall, the secondary metabolites isolated and identified from this plant showed a wide structural diversity ...
C5′-Alkyl Substitution Effects on Digitoxigenin α-l-Glycoside Cancer Cytotoxicity
Hua-Yu Leo Wang, Bulan Wu, Qi Zhang, Sang-Woo Kang, Yon Rojanasakul, and George A. O’DohertyACS Medicinal Chemistry Letters2011 2 (4), 259-263C5′-Alkyl Substitution Effects on Digitoxigenin α-l-Glycoside Cancer Cytotoxicity
Hua-Yu Leo Wang, Bulan Wu, Qi Zhang, Sang-Woo Kang, Yon Rojanasakul, and George A. O’DohertyACS Medicinal Chemistry Letters2011 2 (4), 259-263A highly regio- and stereoselective asymmetric synthesis of various C5′-alkyl side chains of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation with postglycosylated dihydroxylation or diimide ...
Synthesis and Evaluation of the α-d-/α-l-Rhamnosyl and Amicetosyl Digitoxigenin Oligomers as Antitumor Agents
Hua-Yu Leo Wang, Yon Rojanasakul, and George A. O’DohertyACS Medicinal Chemistry Letters2011 2 (4), 264-269Synthesis and Evaluation of the α-d-/α-l-Rhamnosyl and Amicetosyl Digitoxigenin Oligomers as Antitumor Agents
Hua-Yu Leo Wang, Yon Rojanasakul, and George A. O’DohertyACS Medicinal Chemistry Letters2011 2 (4), 264-269A highly regio- and stereoselective asymmetric synthesis of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation followed by bis-/tris-dihydroxylation or bis-/tris-diimide reduction. The α-l-rhamnose ...
Stereochemical Survey of Digitoxin Monosaccharides
Hua-Yu Leo Wang, Wenjun Xin, Maoquan Zhou, Todd A. Stueckle, Yon Rojanasakul, and George A. O'DohertyACS Medicinal Chemistry Letters2011 2 (1), 73-78Stereochemical Survey of Digitoxin Monosaccharides
Hua-Yu Leo Wang, Wenjun Xin, Maoquan Zhou, Todd A. Stueckle, Yon Rojanasakul, and George A. O'DohertyACS Medicinal Chemistry Letters2011 2 (1), 73-78A stereochemically diverse array of monosaccharide analogues of the trisaccharide-based cardiac glycoside natural product digitoxin has been synthesized using a de novo asymmetric approach. The analogues were tested for cytotoxicity against the NCI panel ...
A Direct Comparison of the Anticancer Activities of Digitoxin MeON-Neoglycosides and O-Glycosides
Anand Krishnan V. Iyer, Maoquan Zhou, Neelam Azad, Hosam Elbaz, Leo Wang, Derek K. Rogalsky, Yon Rojanasakul, George A. O'Doherty, and Joseph M. LangenhanACS Medicinal Chemistry Letters2010 1 (7), 326-330A Direct Comparison of the Anticancer Activities of Digitoxin MeON-Neoglycosides and O-Glycosides
Anand Krishnan V. Iyer, Maoquan Zhou, Neelam Azad, Hosam Elbaz, Leo Wang, Derek K. Rogalsky, Yon Rojanasakul, George A. O'Doherty, and Joseph M. LangenhanACS Medicinal Chemistry Letters2010 1 (7), 326-330Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology; however, an investigation of anticancer activity as a function of oligosaccharide chain length has not yet been performed. We generated mono-, di-, and tri-O-...
Tools
-
Add to Favorites
-
Download Citation
-
Email a Colleague -
Permalink
Order Reprints
Rights & Permissions
Citation Alerts
History
- Published In Issue November 28, 2005
- Received June 22, 2005
ACS
Network
Facebook
Tweet This
CiteULike
Newsvine
Digg This
Delicious
