Comparison of the anti‑cancer effect of Disulfiram and 5‑Aza‑CdR on pancreatic cancer cell line PANC‑1

Pancreatic cancer has poor prognosis by surgical and chemotherapy when it is diagnosed, so other anti‑cancerous assistant therapeutic drugs are suggested e.g. epigenetic reversal of tumor‑suppressor genes on promoter hypermethylation. 5‑Aza‑CdR is a nucleoside analog of DNMTi but it has long‑term cytotoxicity effects. This study compares the anticancer effect of 5‑Aza‑CdR and Disulfiram potencies on PANC‑1 cell line and up‑regulation of p21.

PANC‑1 cell line was cultured in DMEM high glucose and treated by 5‑Aza‑CdR with 5 and 10 µM concentration for four days and 13 µM DSF (Diulfiram) for 24 hours. MS‑PCR and RT‑PCR were carried out to detect the methylation pattern and estimate the mRNA expression of RASSF1A and p21 in PANC‑1.

MS‑PCR demonstrated partial unmethylation after treatment with 5‑Aza‑CdR while there was no unmethylated band after DSF treatment. RT‑PCR showed significant differences between re‑expression of RASSF1A before and after treatment with 10 µM 5‑Aza‑CdR (P < 0.01) but not after treatment with 13 µM DSF (P > 0.05). The significant correlation was observed between RASSF1A re‑expression and p21 up‑regulation before and after treatment with 10 µM 5‑Aza‑CdR (P < 0.01) but not after treatment with 13 µM DSF (P > 0.05), while p21 up‑regulation was significantly higher after DSF treatment (P < 0.01).

Our findings indicated that 5‑Aza‑CdR induces the re‑expression of RASSF1A and p21 up‑regulation in PANC‑1. DSF showed no epigenetic reversion while it affected p21 up‑regulation.