Abstract
Tumor metastasis is a major cause of death of patients with colorectal cancer (CRC). Our previous findings show that adenine has antiproliferation activity against tumor cells. However, whether adenine reduces the invasiveness of DLD-1 and SW480 CRC cells has not been thoroughly explored. In this study, we aimed to explore the effects of adenine on the invasion potential of DLD-1 cells. Our findings showed that adenine at concentrations of ≤200 μM did not influence the cell viability of DLD-1 and SW480 CRC cells. By contrast, adenine reduced the migratory potential of the CRC cells. Moreover, it decreased the invasion capacity of the CRC cells in a dose-dependent manner. We further observed that adenine downregulated the protein levels of tissue plasminogen activator, matrix metalloproteinase-9, Snail, TWIST, and vimentin, but upregulated the tissue inhibitor of metalloproteinase-1 expression in DLD-1 cells. Adenine decreased the integrin αV level and reduced the activation of integrin-associated signaling components, including focal adhesion kinase (FAK), paxillin, and Src in DLD-1 cells. Further observations showed that adenine induced AMP-activated protein kinase (AMPK) activation and inhibited mTOR phosphorylation in DLD-1 cells. The knockdown of AMPK restored the reduced integrin αV level and FAK/paxillin/Src signaling inhibited by adenine in DLD-1 cells. Collectively, these findings reveal that adenine reduces the invasion potential of DLD-1 cells through the AMPK/integrin/FAK axis, suggesting that adenine may have anti-metastatic potential in CRC cells.
Highlights
IntroductionColorectal cancer (CRC) is a life-threatening malignancy, and the mortality rates of patients with colorectal cancer (CRC) have increased in the past decade [1]
Our results showed that adenine treatments dose-dependently reduced the transmigration of DLD-1 and SW480 cells to up to 22.3% ± 4.6% and 20.6% ± 3.2% of the control, respectively
Our findings reveal that adenine reduces the transmigration and invasion of DLD-1 and SW480 cells; downregulates the protein expression of metalloproteinase Tissue plasminogen activator (tPA)
Summary
Colorectal cancer (CRC) is a life-threatening malignancy, and the mortality rates of patients with CRC have increased in the past decade [1]. CRC originates from dysplastic adenomatous polyps and gradually transforms into invasive carcinoma after the accumulation of gene mutations that promote proliferation and inhibit epithelial cell apoptosis [2]. The combination of chemotherapy and surgery has been widely and successfully applied to patients with colon cancer, the high recurrence rate and metastasis of CRC lead to the poor survival of patients with advanced CRC [3]. CRC cells escape from the original tumor, spread through the circulating system, and develop a new tumor in other organs or tissues of the body. Migration, and invasion are Pharmaceuticals 2021, 14, 860.
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