Antibiotic Inhibits Cancer Gene Activity

Their findings appear in the Oct. 1 issue of Cancer Research.

"We chose to target a gene believed to be over-expressed in cancer cells to screen for promising anti-cancer agents," said Andrei Gartel, assistant professor of medicine and of microbiology and immunology at UIC and principal investigator on the study.

The FoxM1 gene is responsible for turning on genes needed for cell proliferation and turning off genes that block proliferation. Uncontrolled proliferation is characteristic of cancer cells.

The researchers developed a new screening system, based on a naturally fluorescent protein called luciferase, to identify small molecules that inhibit proteins that turn genes on and off. Using this system, they identified an antibiotic, siomycin A, that specifically targets FoxM1 without affecting other cell functions.

In further experiments in tissue cultures, the researchers found that siomycin A induced cancer cells, but not normal cells, to commit suicide in a process called apoptosis.

The new screening technique, Gartel said, gives researchers a rapid way to find agents that target oncogenes -- genes believed to cause cancer. He said siomycin A, the first compound found with the method, "is particularly promising because we know that it is not toxic."

Siomycin A must now be tested against other cell lines in the laboratory and in preliminary animal experiments before human trials could be planned. Only a tiny fraction of promising candidate drugs enter clinical trials, and few of those are ever approved.

Gartel said the participation of the late Robert Costa, professor of biochemistry and molecular genetics at UIC and a leader in research on FoxM1, was critical for the success of the project thus far.

Senthil Radhakrishnan, a visiting bioinformatics expert at UIC, is first author of the paper. Uppoor Bhat, Douglas Hughes and I-Ching Wang also contributed to the study.

The research was supported by the 2006 Penny Severns Award from the Illinois Department of Public Health, the UIC Department of Medicine and the U.S. Public Health Service.