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Synergistic Effects of Digitoxin Analogues in Combination with Chemotherapeutic Drugs
Author(s) -
Hinds John William,
McKenna Sean
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1014.9
Subject(s) - digitoxin , pharmacology , chemistry , oxaliplatin , doxorubicin , apoptosis , cancer cell , camptothecin , cytotoxicity , cytotoxic t cell , cancer , biochemistry , colorectal cancer , chemotherapy , medicine , heart failure , in vitro , digoxin
Digitoxin is a cardiotonic agent that has traditionally been used as a treatment of congestive heart failure. Recently, it has been acknowledged for its potential in cancer treatment.[1–3] We have characterized a digitoxin‐glycoside, which is believed to express its cytotoxic effect through inhibition of the Na + /K + ‐ATPase pump. This inhibition of Na + /K + exchange by digitoxin is believed to induce apoptosis or programmed cell death selectively in cancer cells via Src‐tyrosine kinase.[4] In previous studies we have synthesized various digitoxin analogues focusing on the stereochemical effects of the C3′/C4′ stereocenters. From this research we identified our lead analogue, α‐L‐rhamno 1.[5] In this study we aim to further the scientific understanding of α‐L‐rhamno 1 and its synergistic effects with other chemotherapeutic agents. The study was conducted on several cancer cell lines using MTT assays to measure cytotoxic effect and to generate dose‐response curves. The drugs chosen to be tested for synergistic or antagonistic effects were selected based on their widely varying mechanisms of action, and conventional use in chemotherapy. These drugs include camptothecin, doxorubicin, oxaliplatin, and 5‐fluorouracil.