Autophagy: novel applications of nonsteroidal anti-inflammatory drugs for primary cancer.

Chen Yu,Wei-Bing Li,Jun-Bao Liu,Ji-Feng Feng,Jian-Wei Lu

doi:10.1002/cam4.1287

Abstract

In eukaryotic cells, autophagy is a process associated with programmed cell death. During this process, cytoplasmic proteins and organelles are engulfed by double‐membrane autophagosomes, which then fuse with lysosomes to form autolysosomes. These autolysosomes then degrade their contents to recycle the cellular components. Autophagy has been implicated in a wide variety of physiological and pathological processes that are closely related to tumorigenesis. In recent years, an increasing number of studies have indicated that nonsteroidal anti‐inflammatory drugs, such as celecoxib, meloxicam, sulindac, aspirin, sildenafil, rofecoxib, and sodium salicylate, have diverse effects in cancer that are mediated by the autophagy pathway. These nonsteroidal anti‐inflammatory drugs can modulate tumor autophagy through the PI3K/Akt/mTOR, MAPK/ERK1/2, P53/DRAM, AMPK/mTOR, Bip/GRP78, CHOP/ GADD153, and HGF/MET signaling pathways and inhibit lysosome function, leading to p53‐dependent G1 cell‐cycle arrest. In this review, we summarize the research progress in autophagy induced by nonsteroidal anti‐inflammatory drugs and the molecular mechanisms of autophagy in cancer cells to provide a reference for the potential benefits of nonsteroidal anti‐inflammatory drugs in cancer chemotherapy.

Highlights

Over the past few decades, much of cancer research has been focused on the mechanisms of apoptosis
The antitumor effects of Nonsteroidal anti-inflammatory drugs (NSAIDs) are related to their autophagy-modulating effects: either activation or inhibition of autophagy
It is important to determine the fate of tumor cells treated with NSAIDs

Summary

Introduction

Over the past few decades, much of cancer research has been focused on the mechanisms of apoptosis. Certain pathways of programmed cell death have been shown to be inhibited either in the presence of autophagic inhibitors or when the expression of the autophagy-specific genes (ATGs) that regulate autophagy is reduced [37, 38]. OSU-0 3012 is a derivative of celecoxib, a COX-2 inhibitor, with anticancer activity that has been shown to induce the death of various types of cancer cells [57].

Results

Conclusion