A novel PPARɣ ligand, PPZ023, overcomes radioresistance via ER stress and cell death in human non-small-cell lung cancer cells

Abstract

Cancer: Reversing resistance to radiotherapy A novel small molecule drug candidate known as PPZ023 could be a powerful anti-cancer agent due to its ability to overcome the resistance of tumors to radiation therapy. Sung Hee Hong and colleagues at the Korea Institute of Radiological and Medical Sciences in Seoul, South Korea, investigated the effects of the molecule on lung cancer cells, including cells that that had acquired resistance to radiotherapy. PPZ023 induces the death of cancer cells by binding to a protein in a known signaling pathway, which generates damaging chemicals known as reactive oxygen species. The researchers identified additional molecular details of the anti-cancer activity. They found the radiotherapy resistance of cancer cells is reversed when PPZ023 promotes cell death via a pathway interfering with the folding of newly formed proteins in a cell structure called the endoplasmic reticulum.