Beclin 1 acetylation impairs the anticancer effect of aspirin in colorectal cancer cells.

Ting Sun,Yunmeng Yan,Liang Ming,Haikuo Xue,Yan Zhang

doi:10.18632/oncotarget.20367

Abstract

Regular use of aspirin can reduce cancer incidence, recurrence, metastasis and cancer-related mortality. Aspirin suppresses proliferation and induces apoptosis and autophagy in colorectal cancer cells, but the precise mechanism is not clear. In this study, we demonstrated that aspirin induced autophagosome formation in colorectal cancer cells, but autophagic degradation was blocked through aspirin-mediated Beclin 1 acetylation. Blocked autophagic degradation weakened aspirin-induced cell death. Collectively, our findings indicate the dual roles of aspirin on autophagy, and demonstrate a new mechanism by which Beclin 1 acetylation impairs the anticancer effect of aspirin in colorectal cancer cells.

Highlights

Aspirin, a nonsteroidal anti-inflammatory drug (NSAID), is widely used as a painkiller, antipyretic or antiplatelet agent for more than 100 years [1]
We demonstrated that aspirin induced autophagosome formation in colorectal cancer cells, but autophagic degradation was blocked through aspirin-mediated Beclin 1 acetylation
There was a striking decrease in the mTORC1 target protein S6K phosphorylation, while phosphorylation of AMPK and ACC was increased after aspirin treatment, confirming aspirin induces AMPK activation and mTOR inhibition in colorectal cancer (CRC) cells (Figure 1B, 1C)

Summary

Introduction

A nonsteroidal anti-inflammatory drug (NSAID), is widely used as a painkiller, antipyretic or antiplatelet agent for more than 100 years [1]. Evidence of aspirin’s anticancer effect is compelling, the underlying molecular mechanism remains enigmatic. Aspirin consists of acetyl and salicylate moieties. While the salicylate group implicates in the antiinflammatory and anti-cancer properties via targeting cyclin A2/CDK2, HMGB1 and NF-κB pathway [11,12,13], the acetyl group causes the inactivation of cyclooxygenases (COXs) through acetylation of serine residues [14]. While aspirin's ability to acetylate and inhibit COXs enzyme activity is well known [14], multiple cellular proteins can be acetylated by aspirin, suggesting that aspirin may exert its anticancer effect by acetylating multiple cellular targets [15, 16]

Methods

Results

Conclusion