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

Abstract

ABSTRACTCancer 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.