Pomegranate Extract Alters Breast Cancer Stem Cell Properties in Association with Inhibition of Epithelial-to-Mesenchymal Transition

ABSTRACT

Cancer stem cells (CSCs) have become an important target population in cancer therapy and prevention due to their ability to self-renew, initiate tumors, and resist therapy. We examined whether pomegranate extract (PE) alters characteristics of breast CSCs. Ability to grow as mammospheres is a hallmark of breast CSCs. PE inhibited mammosphere formation in two different cell lines, neoplastic mammary epithelial HMLER and breast cancer Hs578T. In addition, mammosphere-derived cells from PE treatment groups showed reduced mammosphere formation for at least two serial passages. These data indicate that PE inhibits CSC's ability to self-renew. In addition, incubation of mammospheres with PE reversed them into adherent cultures, indicating promotion of CSC differentiation. Epithelial-to-mesenchymal transition (EMT) is a key program in generating CSCs and maintaining their characteristics. Thus, we examined the effect of PE on EMT. PE reduced cell migration, a major feature of the EMT phenotype. In addition, PE downregulated genes involved in EMT, including the EMT-inducing transcription factor Twist family basic helix-loop-helix transcription factor 1 (TWIST1). This suggests that PE suppresses CSC characteristics in part due to inhibition of EMT. The ability of PE to suppress CSCs can be exploited in the prevention of breast cancer.

Acknowledgments

We wish to thank Dr. JoEllen Welsh (University at Albany, State University of New York) for providing HMLER and Hs578T cells and for assistance with experimental designs. This study was supported by the university's start-up funds.