Down‑expression of poly(ADP‑ribose) polymerase in p53‑regulated pancreatic cancer cells

Abstract

Abstract. The present study investigated whether poly(ADP-ribose) polymerase (PARP) has an effect on p53-regulated pancreatic cancer. The results of the present study demonstrated that the expression of PARP affects proliferation and apoptosis of pancreatic cancer cells. Olaparib was used to suppress the expression level of PARP-1 in PanC-1 cells. Decreased expression of PARP-1 suppressed cell proliferation and induced apoptosis of PanC-1 cells when compared with controls. Furthermore, decreased expression of PARP-1 resulted in decreased levels of pro-caspase-3 expression, increased caspase-3 activity, suppressed B-cell lymphoma 2 (Bcl-2) protein expression and increased p53 protein expression in PanC-1 cells. Subsequently, ataxia telangiectasia mutated (ATM) activity was inhibited alongside down-expression of PARP-1 resulting in significantly decreased cellular viability of PanC-1 cells, increased p53 protein expression, decreased expression of pro-caspase-3, increased caspase-3 activity and suppressed Bcl-2 protein expression, when compared with PARP-1 suppression alone. Overall, the in vitro data confirmed that down-expression of PARP-1 suppressed cell proliferation and induced apoptosis of pancreatic cancer via ATM-deficient p53 signaling pathway.

Electrochemically Reduced Water Delays Mammary Tumors Growth in Mice and Inhibits Breast Cancer Cells Survival In Vitro

“…However, we observed a significant downregulation of the expression of total PARP-1 in MCF-7 and MDA-MB-453 cells. PARP-1 is overexpressed in different types of cancer, including prostate, pancreatic, and breast, and it has been reported that decreased expression of PARP-1 inhibited cell proliferation and induced apoptosis in pancreatic cancer cells [ 62 ]. In addition, the degradation of PARP-1 mediated by caspase-independent ubiquitylation which has a role in apoptosis, necrosis, and other cellular processes has been reported [ 63 – 66 ].…”

CRISPR/Cas9-Mediated Knockdown Of BRCA1/2 Restores Response To Olaparib In Pancreatic Cancer Cell Lines

“…Apoptosis analysis results of the present study have shown an increased apoptosis of pancreatic cells after treatment with 40µM of olaparib, and these differences were found to be statistically signi cant for BRCA KD cells (P < 0.01). In fact olaparib is known to induce apoptosis of cancer cells (44,45). In this respect, our in vitro results suggest that BRCA KD cells may have clinically relevant response to olaparib treatment.…”

Camptothecin loaded casein nanosystem for tuning the therapeutic efficacy against highly metastatic triple-negative breast cancer cells

“…Poly (ADP ribose) polymerase (PARP) is a DNA repair protein that helps cancer cells to reduce stress. 46,47 Downregulation of PARP protein (Fig. 11A and C) was observed with CCS treatment, suggesting irreversible DNA repair and enhanced stress.…”