Phytochemicals Treatment Decreases Drug-Resistant Breast Cancer Stem Cell Viability and Invasiveness by Blocking the HPI/AMF Surviving Pathway

Abstract

The advent of natural phytochemicals for interfering with the HPI/AMF (erythrose, Ery) and TGF-ß (sulforaphane, SP) signaling pathways appears as a promising therapeutic strategy against Breast Cancer Stem Cells (BCSC). The BCSC viability, drug resistance, apoptosis evasion, invasiveness and HPI/AMF signaling axe were analyzed with Ery or SP. HPI/AMF, its downstream targets (H-Ras, p-Akt, p-Erk, NF-kB, p-NF-kB, Wnt/ß-catenin), XIAP, cytokines secretion and the glycoprotein- P increased their contents (2-83 times) in BCSC vs. parental MCF-7 cells. The incubation of BCSC with Ery (80nM/24h) significantly decreased (>85%) the HPI/AMF level, glycoprotein-P, XIAP and the secretion of HPI-AMF/TGF-ß vs. non treated-BCSC, which in turn affected cellular invasiveness. SP (150μM/24h) was unable to affect HPI/AMF axe, although invasiveness was affected (>80%). Ery in combination with SP decreased BCSC viability after 3 days of treatment. These results showed that these phytochemicals are a promising nutrition strategy prompting the design of treatments to blocking cancer relapse induced by CSC.