ART1 silencing enhances apoptosis of mouse CT26 cells via the PI3K/Akt/NF-κB pathway.

Cell Physiol Biochem

Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.

Published: August 2014

AI Article Synopsis

  • Colorectal carcinoma is a common but deadly cancer, and the role of Arginine ADP-ribosyltransferase 1 (ART1) in this disease is not well understood.
  • Researchers silenced ART1 in colon cancer cells and tested how this affected cell survival and apoptosis when treated with cisplatin.
  • The findings indicate that knocking down ART1 increases cancer cell death by reducing survival signaling pathways and altering the balance of pro-apoptotic and anti-apoptotic proteins, highlighting ART1 as a potential target for therapy.

Article Abstract

Background/aims: Colorectal carcinoma is one of the most common cancers world-wide, with high morbidity and mortality rates. Arginine ADP-ribosyltransferase 1(ART1) is an important ecto-ADP-ribose transferase and has been proven to be intimately involved in a number of biological processes. However, the influence of ART1 on survival and apoptosis of colorectal carcinoma cells and the potential mechanism of action of ART1 remain uncharacterized.

Methods: ART1 was silenced via lentiviral vector-mediated short hairpin RNA (shRNA) in CT26 colon carcinoma cells, and cisplatin (CDDP) was applied to induce apoptosis. Survival and apoptosis rate of CT26 cells was assessed by CCK8 assay, flow cytometry and Hoechst 33342 staining. Expression and activity of signaling proteins were detected by Western blot.

Results: ART1 knockdown enhanced the inhibition of cell survival and increased the apoptosis induced by CDDP. Furthermore, the reduced survival rate correlated with reduced levels of phos-Akt(Thr308) and phos-IκBα and reduced NF-κB p65 nuclear translocation. A decline in Bcl-2 and Bcl-xl expression and an increase in Bax expression may explain the enhanced apoptosis.

Conclusion: This study provides a molecular mechanism for the function of ART1 in colorectal carcinoma and defines a potential therapeutic target for the enhanced treatment of this prominent world-wide disease.

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Source
http://dx.doi.org/10.1159/000356595DOI Listing

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