Heartening news for cancer patientsJanuary 6th, 2009 - 3:36 pm ICT by IANS
Washington, Jan 6 (IANS) Drugs like digoxin, used for long to treat patients with irregular heart rhythms and heart failure, also holds promise as treatment for cancer, according to a new study.This finding by Johns Hopkins University (JHU) School of Medicine emerged through a search for existing drugs that might slow or stop cancer progression.
“This is really exciting, to find that a drug already deemed safe by the FDA also can inhibit a protein crucial for cancer cell survival,” said Gregg L. Semenza, director of the vascular programme at the JHU Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine.
Semenza and his team have long studied the hypoxia-inducible factor, or HIF-1, protein, which controls genes that help cells survive under low-oxygen conditions.
HIF-1 turns on genes that grow new blood vessels to help oxygen-starved cells survive. Regions of low oxygen are common within the environment of fast-growing solid tumours.
“Oxygen-deprived cancer cells increase their HIF-1 levels to survive in these unfavourable conditions,” said Semenza. “So turning down or blocking HIF-1 may be key to slowing or stopping these cells from growing.”
The researchers took advantage of the Johns Hopkins Drug Library, a collection of more than 3,000 drugs already FDA approved or currently being tested in phase II clinical trials, assembled by Hopkins pharmacology professor Jun O. Liu.
In this study, the research team tested every drug in the library for its ability to turn down HIF-1in cancer cells. The top 20 candidates identified were able to reduce HIF-1 by more than 88 percent, and more than half of these 20 belong to a class of drugs already commonly used for treating heart failure, and included digoxin.
The researchers focused on digoxin because of its already well-established clinical use. They treated prostate cancer cells grown at normal and low-oxygen levels with digoxin for three days and counted the number of cells each day, said a JHU release.
They found that cells treated with digoxin significantly slowed their growth, with fewer total cells after three days and increased numbers of cells that had stopped growing when compared to untreated cells.
To see if digoxin had the same effect on cancer cells in the physiological context of a whole animal, the team administered daily injections of digoxin to mice with tumours.
In untreated mice, tumours were large enough to be felt within nine days, but in treated mice, tumours could first be felt only after as long as 15 to 28 days.
The team then examined tumours from the mice and found that HIF-1 levels were lower than tumours from untreated mice. The team then went on to show that it is digoxin specifically reducing HIF-1 that leads to the anti-tumour results they saw.
The study was published in the December issue of the Proceedings of the National Academy of Sciences.
Tags: cancer progression, genetic medicine, hypoxia inducible factor, irregular heart rhythms, jhu school, johns hopkins university, oxygen conditions, oxygen levels, pharmacology professor, prostate cancer cells