Asthma Drug Shows Promise for Treating Breast Cancer

A drug in current use for treatment of asthma has performed well in a pre-clinical trial as a potential chemotherapy agent for breast cancer.

The drug, tranilast, has been approved since 1982 for use in Japan and South Korea for treatment of bronchial asthma. It also has been used for the treatment of allergic disorders such allergic rhinitis and atopic dermatitis. It is a relatively safe drug and is well tolerated by most patients at doses of up to 600 mg/day for months.

In the current study, investigators at St. Michael's Hospital (Toronto, Canada) investigated the effect of tranilast on drug resistant breast cancer stem cells growing either in tissue culture or as mouse xenographs. They treated breast cells with mitoxantrone, which caused them to transform into cancer stem cells that expressed the stem cell markers ALDH, c-kit, Oct-4, and ABCG2, and were efficient at forming mammospheres in culture.

The investigators reported in the November 3, 2010, online edition of the journal PLoS ONE that tranilast markedly inhibited mammosphere formation by breast cancer stem cells and dissociated formed mammospheres at pharmacologically relevant concentrations. It was effective against cancer stem cells of both HER-2+ and triple-negative cell lines. Tranilast was also effective in vivo, since it prevented lung metastasis in mice injected with triple-negative mitoxantrone-selected cells

The molecular targets of tranilast in cancer were previously unknown, but in the current study, it was found that it is an aryl hydrocarbon receptor (AHR) agonist. AHR is a transcription factor activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polycyclic aromatic hydrocarbons, and other ligands. Tranilast induced translocation of the AHR to the nucleus and stimulated CYP1A1 expression (a marker of AHR activation). Knockdown of AHR with siRNA, or blockade with an AHR antagonist, entirely eliminated the antiproliferative and antimammosphere activity of tranilast.

"Tranilast, a drug approved for use in Japan and South Korea, and not in use in Canada or the U.S., has been used for more than two decades to treat asthma and other allergic disorders including allergic rhinitis and atopic dermatitis,” said senior author Dr. Gerald Prud'homme, professor of pathology at St. Michael's Hospital. "Now, our study is the first to discover it not only stops breast cancer from spreading but how the drug targets breast cancer cells.”

"For the first time, we were able to show that tranilast shows promise for breast cancer treatment in levels commonly well-tolerated by patients who use the drug for other medical conditions,” Dr. Prud'homme said. "These results are very encouraging and we are expanding our studies. Further studies are necessary to determine if the drug is effective against different types of breast and other cancers, and its interaction with anticancer drugs.”

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