LOS ANGELES (July 21, 1998) -- Breast cancer cells exposed to a diabetes drug and the Vitamin A compound Accutane stopped multiplying and died on cue in laboratory and animal studies conducted at Cedars-Sinai Medical Center, researchers reported today in the journal Proceedings of the National Academy of Science.
Troglitazone, an antidiabetes drug, and Accutane, a Vitamin A compound used to treat severe acne, appear to work synergistically in permanently inhibiting cell growth and inducing apoptosis (programmed cell death) in breast cancer cells.
"Troglitazone alone has a mild effect on breast cancer cells. Accutane alone has a mild effect on breast cancer cells. Together, they have a dramatic effect," said Dr. H. Phillip Koeffler, Director of Hematology/Oncology at Cedars-Sinai Medical Center and Professor of Medicine at the University of California, Los Angeles.
Breast cancer cells stay young and vigorous, proliferating wildly while normal cells around them perform their functions, then mature and die as other cells replace them, Dr. Koeffler explained. The highly selective approach he and his team used not only deprives breast cancer cells of the protein energy source that makes them grow, but also programs them to age and die on schedule.
Importantly, the drug combination appears to have no adverse effect on healthy cells, either in laboratory studies or in immunodeficient mice injected with human breast cells that form tumors.
The way in which the drugs work is not fully understood, although their success is probably due to their targeting of distinct receptors on breast cancer cells that give them an edge over other cells, Dr. Koeffler said.
Troglitazone binds two receptors found in tumor cells: a steroid receptor
called peroxisome proliferator-activated receptor gamma (PPARg), and a retinoid
(Vitamin A) receptor. Accutane may then bind to this combined receptor. The
Contact: Anita Roark
Cedars-Sinai Medical Center