Adenine Inhibits the Growth of Colon Cancer Cells via AMP-Activated Protein Kinase Mediated Autophagy.

Hsin-Wu Lai,Hung-Chang Hung,James Cheng-Chung Wei,Chun-Che Lin

doi:10.1155/2019/9151070

Abstract

Background Adenine is involved in a variety of cell biological processes and has been explored for pharmacological uses. Its therapeutic use for managing cancer is of great interest. In the present study, we investigated the anticancer effects of adenine and the underlying mechanism in colon cancer cells. Methods Cell viability was measured using the MTT assay. Levels of phosphorylation and protein expression were determined using western blotting. qPCR was carried out to determine the changes in mRNA expression of genes of interest. Results Adenine significantly inhibited the viability of colon cancer cells, HT29 and Caco-2 cells, in a dose-dependent manner. Adenine induced significant apoptosis in HT29 cells, whereas Caco-2 cells exhibited less apoptotic responses. The data showed that adenine activated AMP-activated protein kinase (AMPK) signaling contributing to autophagic cell death through mTOR in both colon cancer cell lines. Conclusions Our findings suggest that adenine inhibits the growth of colon cancer cells. Anticancer activity of adenine in colon cancer cells is attributable to the activation of apoptotic signaling and in turn the AMPK/mTOR pathway. Adenine represents a natural compound with anticancer potency.

Highlights

Colorectal cancer (CRC) is one of the leading malignancies, which is expected to account for 2.2 million new cases and 1.1 million deaths worldwide in 2030 [1]
Adenine forms as a component of nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), which are involved in metabolism
We found that AMPK activation was associated with induction of autophagy in presence of adenine; effects of adenine-induced AMPK activation on the growth of colon cancer were investigated. e results showed that increased phosphorylation of AMPK in both colon cancer cell lines treated with adenine were restored in the presence of AMPK inhibitor, dorsomorphin, at a Cleaved caspase‐8

Summary

Introduction

Colorectal cancer (CRC) is one of the leading malignancies, which is expected to account for 2.2 million new cases and 1.1 million deaths worldwide in 2030 [1]. For patients with advanced CRC, treatment options include chemotherapy, radiation therapy, and biological therapy in combination with surgical modalities. These therapeutic regimens achieve somewhat satisfactory local disease control, effective regimens for metastatic CRC patients with liver metastases from colorectal cancer are limited. We investigated the anticancer effects of adenine and the underlying mechanism in colon cancer cells. E data showed that adenine activated AMP-activated protein kinase (AMPK) signaling contributing to autophagic cell death through mTOR in both colon cancer cell lines. Anticancer activity of adenine in colon cancer cells is attributable to the activation of apoptotic signaling and in turn the AMPK/mTOR pathway.

Methods

Results

Conclusion