asthma medication found to work against breast cancer stem cells(including her2+ones)

[Lani]

Asthma drug prevents spread of breast cancer: study
[Eureka News Service]
TORONTO, Ont. — November 1, 2010 — A drug commonly used in Japan and Korea to treat asthma has been found to stop the spread of breast cancer cells traditionally resistant to chemotherapy, according to a new study led by St. Michael's pathologist Dr. Gerald Prud'homme.

"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," Dr. Prud'homme says. "Now, our study is the first to discover it not only stops breast cancer from spreading but how the drug targets breast cancer cells."

Researchers grew breast cancer stem cells, which give rise to other cancer cells, in culture. The cells were injected into two groups of mice, including one group, which was also treated with tranilast. Dr. Prud'homme and his colleagues found the drug reduced growth of the primary cancerous tumour by 50 per cent and prevented the spread of the cancer to the lungs. Researchers also identified a molecule in the cancer cell that binds to tranilast and appears to be responsible for this anti-cancer effect.

Tranilast binds to a molecule known as the aryl hydrocarbon receptor (AHR), which regulates cell growth and some aspects of immunity. This makes the drug beneficial in treating allergies, inflammatory diseases and cancer.

"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 anti-cancer drugs.

OPEN ACCESS: Breast Cancer Stem-Like Cells Are Inhibited by a Non-Toxic Aryl Hydrocarbon Receptor Agonist
[Public Library of Science: One]
Background: Cancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or by sorting of cells expressing CSC markers such as aldehyde dehydrogenase-1 (ALDH). CSCs form colonies in agar, mammospheres in low-adherence cultures, and tumors following xenotransplantation in Scid mice. We hypothesized that tranilast, a non-toxic orally active drug with anti-cancer activities, would inhibit breast CSCs.

Methodology/Findings: We examined breast cancer cell lines or D-CSCs generated by growth of these cells with mitoxantrone. Tranilast inhibited colony formation, mammosphere formation and stem cell marker expression. Mitoxantrone-selected cells were enriched for CSCs expressing stem cell markers ALDH, c-kit, Oct-4, and ABCG2, and efficient at forming mammospheres. Tranilast markedly inhibited mammosphere formation by D-CSCs and dissociated formed mammospheres, at pharmacologically relevant concentrations. It was effective against D-CSCs of both HER-2+ and triple-negative cell lines. Tranilast was also effective in vivo, since it prevented lung metastasis in mice injected i.v. with triple-negative (MDA-MB-231) mitoxantrone-selected cells. The molecular targets of tranilast in cancer have been unknown, but here we demonstrate it is an aryl hydrocarbon receptor (AHR) agonist and this plays a key role. 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). It inhibited binding of the AHR to CDK4, which has been linked to cell-cycle arrest. D-CSCs expressed higher levels of the AHR than other cells. Knockdown of the AHR with siRNA, or blockade with an AHR antagonist, entirely abrogated the anti-proliferative and anti-mammosphere activity of tranilast. Thus, the anti-cancer effects of tranilast are AHR dependent.

Conclusion/Significance: We show that tranilast is an AHR agonist with inhibitory effects on breast CSCs. It is effective against CSCs of triple-negative breast cancer cells selected for anti-cancer drug resistance. These results suggest it might find applications in the treatment of breast cancer.

[DiDi70]

Thank you so much for posting this! It makes me feel so hopeful!

[Julie2]

Looks very promising. I am really tempted to use it for my lung mets. Hope it is available here.

Julie

[caya]

Thanks for posting this hopeful news Lani. I had my hysterectomy at St. Michael's Hospital (downtown Toronto) in 2004 - before BC.

Asthma meds? Wow !!

all the best
caya

[Rich66]

Tranilast/anthranilic acid (Rizaben as Japanese allergy med/CSC killer, w/Gem)

http://her2support.org/vbulletin/sho...ight=Tranilast

[Julie2]

Anybody tried Tranilast? It looks really promising.

Julie

[Jackie07]

Might be the cure we've been looking for since it targets cancer stem cells. Interestingly it mentions about the effectiveness for treating allergy. The three family members (Mom, 2nd Brother, and me) who've been dianosed with cancer are the allergy sufferers in my family (of 8).