The Hydroxyquinoline Analogue YUM70 Inhibits GRP78 to Induce ER Stress-Mediated Apoptosis in Pancreatic Cancer.

ABSTRACT: GRP78 (glucose-regulated protein, 78 kDa) is a key regulator of endoplasmic reticulum (ER) stress signaling. Cancer cells are highly proliferative and have high demand for protein synthesis and folding, which results in significant stress on the ER. To respond to ER stress and maintain cellular homeostasis, cells activate the unfolded protein response (UPR) that promotes either survival or apoptotic death. Cancer cells utilize the UPR to promote survival and growth. In this study, we describe the discovery of a series of novel hydroxyquinoline GRP78 inhibitors. A representative analogue, YUM70, inhibited pancreatic cancer cell growth in vitro and showed in vivo efficacy in a pancreatic cancer xenograft model with no toxicity to normal tissues. YUM70 directly bound GRP78 and i

SUBMITTER: Samanta S 

PROVIDER: S-EPMC8137563 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature