The polyphenolic-rich Aronia melanocarpa juice kills teratocarcinomal cancer stem-like cells, but not their differentiated counterparts

Abstract

A diet rich in plant-derived products is expected to have anticancer chemopreventive effects by acting on the appearance and growth of cancer stem cells (CSCs). Thus the effects of Aronia melanocarpa juice (AMJ) on the mouse embryonal carcinoma (EC) stem cell line P19 were investigated. AMJ inhibited cell proliferation, induced cell cycle arrest in S phase and triggered apoptosis. A pronounced upregulation of tumour suppressors p53 and p73 was observed in association with caspase-3 activation and a downregulation of the anti-apoptotic protein UHRF1 and the stemness factor Oct-4. Overall the results strongly suggest that AMJ is functionally able to counteract the carcinogenesis process by targeting CSCs. Interestingly AMJ selectively kills undifferentiated EC cells, without significant effects on normal restricted pluripotent cells (i.e. NIH/3T3 fibroblasts) or even differentiated EC cells. This argues that a differentiation therapy might normalize the pathological phenotype of a CSC which becomes insensitive to further plant-derived pharmacological treatment.

Keywords

• Polyphenols
• Aronia melanocarpa
• Cancer stem cells
• Differentiation therapy
• Apoptosis
• Oct-4