Phenylacetaldehyde, a volatile flavorand aromacompound, inhibits breast cancer stem cells through the blockade of Stat3/IL-6 signaling pathway

Abstract

Breast cancer is the most common cancer in the world and a major leading cause of cancer deaths in women.Although the availability of diverseeffective therapies hasimproved survival rates,treating breast cancer is still considerable challenges due to the existence of CSCs. CSCs represent capable of treatment resistance, disease recurrence, and metastasis. In this study, we evaluated the PAA, a flavor and aroma volatile compound, for its efficacy to inhibit breast CSCs. Our results showed that PAA treatment significantly inhibited breast cancer cell proliferation, migration and colony formation. In addition, PAA induced the apoptosis of breast cancer cells and suppressed tumor growth in vivo.PAA reduced the mammosphere forming ability of breast cancer cells, the CD44high/CD24lowsubpopulationand the percentage of ALDH+cells. PAA also decreasedthe expression of self-renewal genesincluding Nanog, Sox2, Oct4 and CD44 as well as induced ROS activity. Furthermore, PAA blocked the Stat3 signaling pathway viainhibition ofnuclear Stat3 phosphorylationand IL-6secretion. Taken together, our findings suggest that PAA has anti-cancer and anti-CSC activitiesin breast cancer cells.This study provides evidence that PAA may improve the limitedeffects of breast cancer therapy.