Role of UPR Sensor Activation in Cell Death–Survival Decision of Colon Cancer Cells Stressed by DPE Treatment
Rossella Benedetti, Maria Saveria Gilardini Montani, Maria Anele Romeo, Andrea Arena, Roberta Santarelli, Gabriella D’Orazi, Mara Cirone
Abstract
Polyphenols have been shown to possess several beneficial properties, including properties involved in the prevention or treatment of cancer. Among these polyphenols, a leading role is played by dihydroxyphenylethanol (DPE), the most powerful antioxidant compound contained in the olive oil. DPE has been previously reported to induce endoplasmic reticulum (ER) stress and to reduce cell survival in colon cancer, one of the most common and aggressive cancers in developed countries. In this study, we further investigated the activation of UPR by DPE and explored the roles of the three UPR sensors, inositol-requiring enzyme (IRE) 1 alpha, protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor (ATF6), in the cell death-survival decision of wt and mutp53 colon cancer cells and the underlying mechanisms involved. We also unveiled a new interplay between ATF6 and wt, as well as mutp53, which may have important implications in cancer therapy.