Poster Presenter

Tranilast Targets Breast Cancer Stem Cells
Prud’homme GJ, Glinka Y, Toulina A, Subramaniam V and Jothy S
Canada

Cancer stems cells (CSCs) have increased resistance to anti-cancer drugs, and may be a cause therapeutic failure. CSCs can be enriched from cancer cell lines by growth with anti-cancer drugs (doxorubicin, mitoxantrone), and form mammospheres in culture. We are studying tranilast, a non-toxic orally active drug in clinical use for allergic diseases, but that we found targets breast cancer cells. We found that tranilast inhibits the following: cell cycling, TGF-beta activity, MAPK signalling, epithelial-to-mesenchymal transition, cell migration and invasion. In vivo, it has prominent anti-metastatic effects. Our recent studies show that tranilast strongly inhibits CSCs in several assays, at pharmacologically relevant concentrations. We recently identified molecular targets of this drug. We found it has aryl hydrocarbon receptor (AHR) agonist activity in CSCs, and this may explain its anti-cancer effects. Moreover, we found it inhibits some ATP-binding cassette (ABC) multiple drug resistance transporters. In accord with this, it enhances the effects of other anti-cancer drugs. Our studies show that tranilast has potential as an anti-CSC drug