Synergistic effect of arginine-specific ADP-ribosyltransferase 1 and poly(ADP-ribose) polymerase-1 on apoptosis induced by cisplatin in CT26 cells

Abstract

Arginine-specific ADP-ribosyltransferase 1 (ART1) and poly(ADP-ribose) polymerase-1 (PARP-1) are both post‑translational modification proteins. Inhibition of PARP1 induces apoptosis in cancer cells, and ART1 regulates RhoA which promotes apoptosis in hepatic cancer cells when inhibited. However, the interaction of ART1 and PARP-1 on the effect of apoptosis has not yet been elucidated. In the present study, lentiviral vector-mediated ART1-cDNA was transfected into CT26 cells, and the apoptosis rate was detected by flow cytometric assay and Hoechst 33342 staining. Relevant factors were detected by reverse transcriptase-PCR and western blotting. The results showed that the apoptosis rate in the ART1-cDNA CT26 cells treated with PARP-1 inhibitor 5-aminoisoquinoline (5-AIQ) and cisplatin increased, when compared with the ART1-cDNA CT26 cells treated with cisplatin only or the untreated ART1-cDNA CT26 cells. Further studies have shown that PARP-1 is in the downstream of ART1, and plays a role in ART1-mediated CT26 cell apoptosis through the ROCK1/NF-κB/PARP-1 pathway when induced by cisplatin. We also found that in cisplatin-treated cells, activated caspase 3 cleaved PARP-1 and the decreased level of PARP-1 in turn decreased the expression of nuclear factor (NF)-κB, Cox-2 and increased caspase 3, resulting in the enhanced ability of ART1 to regulate CT26 cell apoptosis. Our research provides initial sight into the synergistic effect of ART1 and PARP-1 on apoptosis induced by cisplatin in murine colon carcinoma CT26 cells.